Huaier Extract Attenuates Acute Kidney Injury to Chronic Kidney Disease Transition by Inhibiting Endoplasmic Reticulum Stress and Apoptosis via miR-1271 Upregulation

Biomed Res Int. 2020 Dec 10;2020:9029868. doi: 10.1155/2020/9029868. eCollection 2020.　　I F 3.411 

Authors

Jing-Ying Zhao  ¹ , Yu-Bin Wu  ¹

Affiliation

• ¹ Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
• PMID: 33457422
• PMCID: PMC7787756
• DOI: 10.1155/2020/9029868

Free PMC article

Abstract

Endoplasmic reticulum stress (ERS) is strongly associated with acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Huaier extract (HE) protects against kidney injury; albeit, the underlying mechanism is unknown. We hypothesized that HE reduces kidney injury by inhibiting ERS. In this study, using an AKI-CKD mouse model of ischemia-reperfusion injury (IRI), we evaluated the effect of HE on AKI-CKD transition. We also explored the underlying molecular mechanisms in this animal model and in the HK-2 human kidney cell line. The results showed that HE treatment improved the renal function, demonstrated by a significant decrease in serum creatinine levels after IRI. HE appreciably reduced the degree of kidney injury and fibrosis and restored the expression of the microRNA miR-1271 after IRI. Furthermore, HE reduced the expression of ERS markers glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) and inhibited apoptosis in the IRI group. This in vivo effect was supported by in vitro results in which HE inhibited apoptosis and decreased the expression of CHOP and GRP78 induced by ERS. We demonstrated that CHOP is a target of miR-1271. In conclusion, HE reduces kidney injury, probably by inhibiting apoptosis and decreasing the expression of GRP78 and CHOP via miR-1271 upregulation.

Copyright © 2020 Jing-Ying Zhao and Yu-Bin Wu.

Conflict of interest statement

The authors declare no conflicts of interest.

• Cited by 1 article
• 34 references
• 5 figures

Anti-tumor effect of Huaier extract against neuroblastoma cells in vitro

Int J Med Sci. 2021 Jan 1;18(4):1015-1023. doi: 10.7150/ijms.48219. eCollection 2021.　I F 3.738

Authors

Dong-Qing Xu  ^1   2 , Xiao-Jun Yuan  ¹ , Hidemi Toyoda  ² , Masahiro Hirayama  ²

Affiliations

• ¹ Department of Pediatric Hematology/Oncology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
• ² Department of Pediatrics, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu, Mie, Japan.
• PMID: 33456359
• PMCID: PMC7807190
• DOI: 10.7150/ijms.48219

Free PMC article

Abstract

Huaier extract, the main active constituent proteoglycan, has anti-tumor activity in various experimental and clinical settings. However, the potential anti-neuroblastoma and associated mechanisms have not been investigated. Therefore, in this study, we aimed to elucidate the potential role of Huaier extract in 3 human neuroblastoma cell lines. Our study demonstrated that incubation with Huaier extract resulted in a marked decrease in cell viability in a dose-dependent manner. Huaier extract induced cell cycle arrest at G0/G1 phase in neuroblastoma and decreased the cell cycle related protein expression of cyclin D3. Western blotting analysis also showed that Huaier extract induced neuroblastoma cell apoptosis and autophagy. Signaling analysis indicated that Huaier extract suppressed the MEK/ERK and mTOR signaling pathways simultaneously. In conclusion, we verify that Huaier extract causes cell proliferation inhibition, apoptosis, autophagy, and cell cycle arrest in G0/G1 phase via MEK/ERK and mTOR signaling. Huaier extract may act as a complementary agent for treating neuroblastoma.

Keywords: Apoptosis; Huaier Extract; MEK/ERK; Neuroblastoma; mTOR.

© The author(s).

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

• Cited by 2 articles
• 28 references
• 5 figures

Systematic evaluation of Huaier Granules adjuvant treatment of primary liver cancer

Zhongguo Zhong Yao Za Zhi. 2021 Jan;46(2):478-487. doi: 10.19540/j.cnki.cjcmm.20200716.502.　I F 0.449

[Article in Chinese]

Authors

Rong-Rong Zhang  ¹ , Ming-Yi Shao  ² , Yu Fu  ² , Rui-Xia Zhao  ² , Jing-Wen Wang  ¹ , Man Li  ¹, Yun-Xia Zhao  ¹ , Fan-Lei Shao  ¹

Affiliations

• ¹ Henan University of Traditional Chinese Medicine Zhengzhou 450046, China.
• ² the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Henan Center for Evidence-based Medicine of Traditional Chinese Medicine Zhengzhou 450000, China.
• PMID: 33645137
• DOI: 10.19540/j.cnki.cjcmm.20200716.502

Abstract

To systematically evaluate the efficacy and safety of Huaier Granules in the adjuvant treatment of primary liver cancer. The databases of CNKI, Wanfang, VIP, CBMdisc, PubMed, Cochrane Library and EMbase were searched by computer to screen out the randomized controlled trial on Huaier Granules combined with Western medicine in the treatment of primary liver cancer from the establishment of the databases to January 2020. Data extraction and quality evaluation were conducted for the included literature. Meta-analysis was conducted with RevMan 5.3 software, and evidence quality evaluation was conducted for the outcomes by GRADE profiler software. A total of 24 articles were included, with a total sample size of 2 664 cases. Meta-analysis showed that as compared with Western medicine alone, Huaier Granules combined with Western medicine could improve the objective remission rate(RR=1.38, 95%CI[1.26, 1.51], P<0.000 01), disease control rate(RR=1.29, 95%CI[1.10, 1.52], P=0.002) and 6-month survival rate(RR=1.20, 95%CI[1.10, 1.32], P<0.000 1), 1-year survival rate(RR=1.39, 95%CI[1.23, 1.58], P<0.000 01), 2-year survival rate(RR=1.95, 95%CI[1.28, 2.96], P=0.002), KPS score(MD=17.15, 95%CI[6.47, 27.83], P=0.002) and the improvement rate of KPS score(RR=2.02, 95%CI[1.47, 2.77], P<0.000 1), AFP decline rate(RR=1.40, 95%CI[1.20, 1.62], P<0.000 1), CD3~+(MD=17.34, 95%CI[9.28, 25.40], P<0.000 1), CD4~+(MD=8.62, 95%CI[1.59, 15.64], P=0.02), CD8~+(MD=1.95, 95%CI[-3.93, 7.82], P=0.52), CD4~+/CD8~+(MD=0.42, 95%CI[-0.33, 1.17], P=0.27); reduce the level of AFP(MD=-71.57, 95%CI[-80.42,-62.72], P<0.000 01), recurrence rate(RR=0.76, 95%CI[0.67, 0.85], P<0.000 01), and incidence of adverse reactions(RR=0.60, 95%CI[0.41, 0.89], P=0.01) in patients with primary liver cancer. According to the GRADE system, the evidence for outcome measures was low to very low. The results show that Huaier Granules have certain efficacy and high safety in adjuvant treatment of primary liver cancer, but its effect in reducing adverse reactions and improve immunity remains to be verified. Due to the poor quality of the included studies and evidences, the conclusions still need to be further verified by multi-center, large sample, and randomized double-blind controlled studies.

Keywords: Huaier Granules; Meta-analysis; efficacy; primary liver cancer; safety; systematic evaluation.

• Cited by 2 articles

Huaier Inhibits Proliferation, Migration, and Invasion of Cutaneous Squamous Cell Carcinoma Cells by Inhibiting the Methylation Levels of CDKN2A and TP53

Integr Cancer Ther. 2021 Jan-Dec;20:15347354211031646. doi: 10.1177/15347354211031646.　I F 3.279

Authors

Liang Wang  ¹ , Lei Xu  ¹ , Yu Wang  ¹

Affiliation

• ¹ Department of Dermatology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
• PMID: 34291682
• PMCID: PMC8312153
• DOI: 10.1177/15347354211031646

Free PMC article

Abstract

Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor that originates from keratinocytes in the epidermis or appendage. Traditional Chinese medicine Huaier has anti-tumor activity in various malignancies. Little is known about the role of Huaier in CSCC. Here, we investigated the function of Huaier in CSCC. We treated CSCC cell line (SCL-1 and A431) with a series of concentration gradients of Huaier to examine the half maximal inhibitory concentration (IC50) of Huaier on SCL-1 and A431 cells. The IC50 of Huaier on growth of SCL-1 and A431 cells were 6.96 and 7.57 mg/mL, respectively. Moreover, Huaier reduced the methylation levels of CDKN2A and TP53, and enhanced the expression of CDKN2A and TP53 in SCL-1 and A431 cells in a dosage-dependent manner. The expression of DNA methyltransferase DNMT1 was severely repressed by Huaier treatment in SCL-1 and A431 cells. DNMT1 overexpression enhanced the methylation levels of CDKN2A and TP53, and suppressed the expression of CDKN2A and TP53 in Huaier-treated SCL-1 and A431 cells. Huaier treatment inhibited proliferation, migration, and invasion of SCL-1 and A431 cells. However, inhibition of CDKN2A or TP53 reversed the influence of Huaier treatment on proliferation, migration, and invasion of CSCC cells. In conclusion, our data demonstrate that Huaier inhibits proliferation, migration, and invasion of CSCC cells by regulating DNA methylation of CDKN2A and TP53, thereby attenuating the progression of CSCC. Thus, Huaier extract may act as a drug for treating CSCC.

Keywords: CDKN2A; DNA methylation; Huaier; TP53; cutaneous squamous cell carcinoma.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

• 28 references
• 3 figures

Huaier extract suppresses non-small cell lung cancer progression through activating NLRP3-dependent pyroptosis

Anat Rec (Hoboken). 2021 Feb;304(2):291-301. doi: 10.1002/ar.24307. Epub 2019 Nov 22.　I F 2.064

Authors

Jun Xie  ¹ , Bing Zhuan  ² , Haixia Wang  ³ , Yan Wang  ² , Xi Wang  ³ , Qun Yuan  ³ , Zhao Yang  ³

Affiliations

• ¹ Department of Thoracic Surgery, Suzhou Science & Technology Town Hospital, Suzhou, China.
• ² Department of Respiratory Medicine, The First Affiliated Hospital of Northwest University for Nationalities, Yinchuan, China.
• ³ Department of Respiratory Medicine, Suzhou Science & Technology Town Hospital, Suzhou, China.
• PMID: 31692261
• DOI: 10.1002/ar.24307

Free article

Retraction in

• Retraction.

[No authors listed]

Anat Rec (Hoboken). 2021 Dec;304(12):2899. doi: 10.1002/ar.24811. Epub 2021 Oct 28.

PMID: 34708945No abstract available.

Abstract

Recent studies have reported the anticancer activity of huaier extract in various human malignancies. However, little is known about the effect of huaier extract in non-small cell lung cancer (NSCLC) and its underlying mechanism. The current study aimed to investigate whether huaier extract affects the progression of NSCLC. mRNA and proteins expression of pyroptotic-related genes (NLRP3, caspase-1, IL-1β, and IL-18) in NSCLC tissues and cells were, respectively, detected by qRT-PCR and western blot. The effects of huaier extract on NSCLC cell viability and cytotoxicity were evaluated by CCK-8 assay, colony formation assay, and LDH detection kit. Besides, we established a xenograft model to assess the antitumor effect of huaier extract on tumor growth in vivo. Our results showed that the expression of pyroptotic-related genes was downregulated in NSCLC tissues and cell lines. Huaier extract pretreatment inhibited cell viability and the percentage of colony formation of H520 and H358 cells, and upregulated the expression of pyroptotic-related genes. Mechanistically, huaier extract exhibited antitumor effect in NSCLC via inducing NLRP3-dependent pyroptosis in vitro and in vivo. In conclusion, our finding confirmed that huaier extract played an antitumor role in NSCLC progression through promoting pyroptotic cell death, which provided a new potential strategy for NSCLC clinical treatment.

Keywords: NLRP3; huaier; non-small cell lung cancer; pyroptosis.

© 2019 American Association for Anatomy.

• Cited by 17 articles
• 48 references

Huaier shows anti-cancer activities by inhibition of cell growth, migration and energy metabolism in lung cancer through PI3K/AKT/HIF-1α pathway

J Cell Mol Med. 2021 Feb;25(4):2228-2237. doi: 10.1111/jcmm.16215. Epub 2020 Dec 30.　I F 5.31

Authors

Xiangli Liu  ¹ , Lidan Liu  ² , Keyan Chen  ³ , Lei Sun  ¹ , Wenya Li  ¹ , Shuguang Zhang  ¹

Affiliations

• ¹ Department of Thoracic Surgery, the First Affiliated Hospital of China Medical University, Shenyang, China.
• ² Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China.
• ³ Department of Laboratory Animal Science, China Medical University, Shenyang, China.
• PMID: 33377619
• PMCID: PMC7882940
• DOI: 10.1111/jcmm.16215

Free PMC article

Abstract

Huaier has been verified to have anti-cancer effects on many tumours. However, little information is available about the effects of Huaier on non-small cell lung cancer (NSCLC). We sought to probe the anti-cancer effects and related mechanisms of Huaier on lung cancer. A549 cells were pre-treated with 2, 4 and 8 mg/mL Huaier at different time points. Thereafter, cell viability was analysed by CCK-8 and the migration and invasion were detected by Scratch test and Transwell chamber migration assay. Moreover, ELISA, Western blot, shRNA transfection and RT-PCR were conducted to discover the related gene and protein expressions of energy metabolism and phosphatidylinositol 3-kinase (PI3K)/AKT/hypoxia-inducible factor 1α (HIF-1α) pathway. Furthermore, tumour xenografts were accomplished to inspect the anti-cancer effects of Huaier. Our consequences suggested that Huaier considerably repressed cell viability and migration in a dose-dependent way. In addition, Huaier statistically suppressed glycolysis, glucose transport and lactic acid (LA) accumulation. Besides, we detected that Huaier could inactivate the PI3K/AKT/HIF-1α pathway. The in vivo data confirmed that Huaier obviously decreased tumour volume and tumour growth, reduced the glycolysis, glucose transport and HIF-1α expression in the tumour-bearing tissues. Our results suggested Huaier revealed anti-tumour effects in both in vivo and in vitro possibly through PI3K/AKT/HIF-1α pathway.

Keywords: AKT; HIF-1α pathway; Huaier; NSCLC; PI3K; energy metabolism.

© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Conflict of interest statement

The authors declare that they have no conflicts of interest.

• Cited by 5 articles
• 48 references
• 7 figures

Huaier Extract Inhibits Prostate Cancer Growth viaTargeting AR/AR-V7 Pathway

Front Oncol. 2021 Feb 23;11:615568. doi: 10.3389/fonc.2021.615568. eCollection 2021.　I F 6.244

Authors

Zhengfang Liu  ¹ , Cheng Liu  ² , Keqiang Yan  ¹ , Jikai Liu  ¹ , Zhiqing Fang  ^1   3 , Yidong Fan  ¹

Affiliations

• ¹ Department of Urology, Qilu Hospital of Shandong University, Ji’nan, China.
• ² Department of Urology, Peking University Third Hospital, Beijing, China.
• ³ Department of Medicine, Center for Molecular Medicine (CMM) and Bioclinicum, Karolinska Institute and Karolinska University Hospital Solna, Solna, Sweden.
• PMID: 33708629
• PMCID: PMC7940541
• DOI: 10.3389/fonc.2021.615568

Free PMC article

Abstract

The androgen receptor (AR) plays a pivotal role in prostatic carcinogenesis, and it also affects the transition from hormone sensitive prostate cancer (HSPC) to castration-resistant prostate cancer (CRPC). Particularly, the persistent activation of the androgen receptor and the appearance of androgen receptor splicing variant 7 (AR-V7), could partly explain the failure of androgen deprivation therapy (ADT). In the present study, we reported that huaier extract, derived from officinal fungi, has potent antiproliferative effects in both HSPC and CRPC cells. Mechanistically, huaier extract downregulated both full length AR (AR-FL) and AR-V7 mRNA levels via targeting the SET and MYND domain-containing protein 3 (SMYD3) signaling pathway. Huaier extract also enhanced proteasome-mediated protein degradation of AR-FL and AR-V7 by downregulating proteasome-associated deubiquitinase ubiquitin-specific protease 14 (USP14). Furthermore, huaier extract inhibited AR-FL/AR-V7 transcriptional activity and their nuclear translocation. More importantly, our data demonstrated that huaier extract could re-sensitize enzalutamide-resistant prostate cancer cells to enzalutamide treatment in vitro and in vivo models. Our work revealed that huaier extract could be effective for treatment of prostate cancer either as monotherapy or in combination with enzalutamide.

Keywords: androgen receptor splicing variant 7 (AR-V7); enzalutamide; full length androgen receptor (AR-FL); huaier extract; prostate cancer.

Copyright © 2021 Liu, Liu, Yan, Liu, Fang and Fan.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

• Cited by 3 articles
• 54 references
• 7 figures

p-MEK expression predicts prognosis of patients with adenocarcinoma of esophagogastric junction (AEG) and plays a role in anti-AEG efficacy of Huaier

Pharmacol Res. 2021 Mar;165:105411. doi: 10.1016/j.phrs.2020.105411. Epub 2021 Jan 2.　I F 10.334

Authors

Li Yuan  ¹ , Shao-Wei Mo  ² , Zhi-Yuan Xu  ³ , Hang Lv  ⁴ , Jing-Li Xu  ² , Kai-Bo Guo  ² , Can Hu ² , Xiao-Feng Wang  ² , Gui-Ping Chen  ⁴ , Jiang-Jiang Qin  ⁵ , Xiang-Dong Cheng  ⁶

Affiliations

• ¹ The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China; First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.
• ² First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.
• ³ The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China.
• ⁴ Department of Gastrointestinal Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China.
• ⁵ The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China. Electronic address: zylysjtu@hotmail.com.
• ⁶ The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China. Electronic address: chengxd516@126.com.
• PMID: 33401002
• DOI: 10.1016/j.phrs.2020.105411

Abstract

The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide with poor prognosis and unclear pathogenesis. Trametes robiniophila Murr. (Huaier), a traditional Chinese medicine has been used in the clinical treatment of a variety of solid tumors, including AEG. However, its anticancer components and molecular mechanisms are still unclear. In our previous studies, we have found that Huaier n-butanol extract (HBE) shows the most potent anticancer activity among different extracts. In the present study, we aimed to investigate the clinical relevance of p-MEK expression in AEG patients and the role of the MEK/ERK signaling pathway in the anti-AEG efficacy of HBE in vitro and in vivo. We herein demonstrate that p-MEK expression in AEG tissues was significantly higher than that in paracancerous tissues and correlated with a poor prognosis in AEG patients. We further found that HBE inhibited the colony formation, migration, and invasion in AEG cell lines in a concentration-dependent manner in vitro. HBE also suppressed the growth of AEG xenograft tumors without causing any host toxicity in vivo. Mechanistically, HBE caused the inactivation of the MEK/ERK signaling pathway by dephosphorylating MEK1 at S298, ERK1 at T202, and ERK2 at T185 and modulating the expression of EMT-related proteins. In summary, our results demonstrate that the high expression of p-MEK may be an independent factor of poor prognosis in patients with AEG. The clinically used anticancer drug Huaier may exert its anti-AEG efficacy by inhibiting the MEK/ERK signaling pathway.

Keywords: Adenocarcinoma of the esophagogastric junction; Huaier; Invasion and metastasis; MEK/ERK signaling pathway; p-MEK.

Copyright © 2021 Elsevier Ltd. All rights reserved.

• Cited by 5 articles

Huaier increases the antitumor effect of gemcitabine on pancreatic cancer in vitro and in vivo

Transl Cancer Res. 2021 Mar;10(3):1368-1377. doi: 10.21037/tcr-20-2627.　I F 1.241

Authors

Tao Chen ^#  1 , Dongbao Li ^{#  1   2   3} , Chao Feng ^#  4 , Zixiang Zhang  ¹ , Dongming Zhu  ¹, Dechun Li  ¹ , Xin Zhao  ^{1   2   3}

Affiliations

• ¹ Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
• ² Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China.
• ³ Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, China.
• ⁴ Soochow University Institutes for Translational Medicine, Suzhou, China.

^# Contributed equally.

• PMID: 35116462
• PMCID: PMC8799115
• DOI: 10.21037/tcr-20-2627

Free PMC article

Abstract

Background: Pancreatic cancer has a high degree of malignancy and poor prognosis. As the first-line chemotherapy drug for pancreatic cancer, gemcitabine is widely used but is limited in its efficacy due to the development of chemoresistance. Huaier is a traditional Chinese medicine with anticancer effects. This present study explored the antitumor effect of gemcitabine combined with Huaier on pancreatic cancer in vitro and in vivo.

Methods: After treatment with gemcitabine combined with Huaier in PaTu8988 pancreatic cancer cells, including 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, wound healing, and Transwell invasion in vitro assays were performed to investigate the proliferation, migration and invasion of cells, respectively. The apoptotic rate of cells was detected by propidium iodide-annexin V staining and flow cytometry. In vivoPaTu8988 pancreatic cancer xenograft and tail vein injection into lung metastasis nude mice models were used to determine the tumor growth and lung metastasis efficiency.

Results: Huaier could not only inhibit the proliferation, migration, and invasion of cancer cells, but could also induce the apoptosis of pancreatic cancer in vitro and suppress tumor growth and lung metastasis in vivo. It further significantly increased the tumor suppressing effects of gemcitabine, and combined use of the two drugs exhibited a synergistic effect.

Conclusions: Our present study concluded that Huaier was capable of enhancing the antitumor effect of gemcitabine in pancreatic cancer in vitro and in vivo. Therefore, Huaier may be a potential drug to increase the therapy sensitivity of gemcitabine and improve the prognosis of pancreatic cancer patients.

Keywords: Huaier; antitumor; gemcitabine; pancreatic cancer; traditional Chinese medicine (TCM).

2021 Translational Cancer Research. All rights reserved.

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-20-2627). The authors have no conflicts of interest to declare.

• 36 references
• 4 figures   

Adjuvant treatment strategy after curative resection for hepatocellular carcinoma

Front Med. 2021 Apr;15(2):155-169. doi: 10.1007/s11684-021-0848-3. Epub 2021 Mar 23.　I F 4.592

Authors

Wei Zhang  ¹ , Bixiang Zhang  ² , Xiao-Ping Chen  ³

Affiliations

• ¹ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
• ² Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. bixiangzhang@163.com.
• ³ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. chenxpchenxp@163.com.
• PMID: 33754281
• DOI: 10.1007/s11684-021-0848-3

Abstract

Hepatic resection represents the first-line treatment for patients with resectable hepatocellular carcinoma (HCC). However, the 5-year recurrence rates of HCC after surgery have been reported to range from 50% to 70%. In this review, we evaluated the available evidence for the efficiency of adjuvant treatments to prevent HCC recurrence after curative liver resection. Antiviral therapy has potential advantages in terms of reducing the recurrence rate and improving the overall survival (OS) and/or disease-free survival of patients with hepatitis-related HCC. Postoperative adjuvant transarterial chemoembolization can significantly reduce the intrahepatic recurrence rate and improve OS, especially for patients with a high risk of recurrence. The efficacy of molecular targeted drugs as an adjuvant therapy deserves further study. Adjuvant adoptive immunotherapy can significantly improve the clinical prognosis in the early stage. Randomized controlled trial (RCT) studies evaluating adjuvant immune checkpoint inhibitors are ongoing, and the results are highly expected. Adjuvant hepatic artery infusion chemotherapy might be beneficial in patients with vascular invasion. Huaier granule, a traditional Chinese medicine, has been proved to be effective in prolonging the recurrence-free survival and reducing extrahepatic recurrence. The efficiency of other adjuvant treatments needs to be further confirmed by large RCT studies.

Keywords: adjuvant treatment; hepatic resection; hepatocellular carcinoma; recurrence.

• Cited by 5 articles
• 156 references

Network Meta-analysis of oral Chinese patent medicine for adjuvant treatment of primary liver cancer

Zhongguo Zhong Yao Za Zhi. 2021 May;46(9):2333-2343. doi: 10.19540/j.cnki.cjcmm.20200721.501.　 I F 0.449

[Article in Chinese]

Authors

Rong-Rong Zhang  ¹ , Ming-Yi Shao  ² , Yu Fu  ² , Rui-Xia Zhao  ² , Jing-Wen Wang  ¹ , Man Li  ¹, Yun-Xia Zhao  ¹ , Fan-Lei Shao  ¹

Affiliations

• ¹ Henan University of Chinese Medicine Zhengzhou 450046, China.
• ² the First Affiliated Hospital of Henan University of Chinese Medicine, Henan Center for Evidence-based Medicine of Traditional Chinese Medicine Zhengzhou 450000, China.
• PMID: 34047138
• DOI: 10.19540/j.cnki.cjcmm.20200721.501

Abstract

Network Meta-analysis was used to evaluate the efficacy and safety of different oral Chinese patent medicines combined with transcatheter arterial chemoembolization(TACE) in the treatment of primary liver cancer. Randomized controlled trials of oral Chinese patent medicines for primary liver cancer were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library and EMbase databases from inception to May 2020. According to the Cochrane recommendation standard, the quality of the included articles was evaluated, and the data were analyzed by RevMan, R software and GeMTC software. A total of 10 kinds of oral Chinese patent medicines and 68 RCTs were included. Network Meta-analysis results showed that: as compared with TACE alone, 10 kinds of oral Chinese patent medicines combined with TACE showed advantages in effective rate, 1-year survival rate, 2-year survival rate, KPS score improvement rate and reduced adverse reaction incidence. In the pairwise comparison of oral Chinese patent medicines, the results showed that Cidan Capsules were superior to Jinlong Capsules and Xihuang Pills in 1-year survival rate. According to the probabi-lity ranking results: Shenyi Capsules and Ganfule were more obvious in improving the effective rate; Cidan Capsules and Shenyi Capsules were more effective in improving the 1-year survival rate; Pingxiao Capsules and Shenyi Capsules had better efficacy in improving 2-year survival rate; Huaier Granules and Shenyi Capsules had better efficacy in improving the quality of life; Huisheng Oral Liquid and Ganfule were more effective in reducing the incidence of adverse reactions(such as nausea, vomiting and leukocytosis). The current evidence showed that oral Chinese patent medicine combined with TACE was superior to TACE alone in efficacy and safety. In terms of the effective rate, 1-year survival rate, 2-year survival rate, KPS score improvement rate and reduced adverse reaction incidence, the optimal treatment measures were Shenyi Capsules, Cidan Capsules, Pingxiao Capsules, Huaier Granules and Huisheng Oral Liquid in turn. However, due to the limitations of the research, the current level of evidence is not high, and clear conclusions and evi-dence strength still need to be further verified and improved by high-quality researches.

Keywords: network Meta-analysis; oral Chinese patent medicine; primary liver cancer; transcatheter artery chemoembolization.

Complete Response of Hepatocellular Carcinoma with Macroscopic Vascular Invasion and Pulmonary Metastasis to the Combination of Drug-Eluting Beads Transarterial Chemoembolization and Huaier Granule: A Case Report

Onco Targets Ther. 2021 Jun 23;14:3873-3880. doi: 10.2147/OTT.S309660. eCollection 2021.　I F 4.147

Authors

Tan-Yang Zhou  ^1   2 , Guo-Fang Tao  ³ , Sheng-Qun Chen  ^1   2 , Hong-Liang Wang  ^1   2 , Yue-Lin Zhang  ^1   2 , Guan-Hui Zhou  ^1   2 , Chun-Hui Nie  ^1   2 , Tong-Yin Zhu  ^1   2 , Bao-Quan Wang  ^1  2 , Zi-Niu Yu  ^1   2 , Li Jing  ^1   2 , Feng Chen  ⁴ , Jun-Hui Sun  ^{1   2   5}

Affiliations

• ¹ Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang Province, People’s Republic of China.
• ² Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, 310003, Zhejiang Province, People’s Republic of China.
• ³ Department of Respiratory Medicine, Thoracic Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang Province, People’s Republic of China.
• ⁴ Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China.
• ⁵ Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, 310003, Zhejiang Province, People’s Republic of China.
• PMID: 34188493
• PMCID: PMC8236259
• DOI: 10.2147/OTT.S309660

Free PMC article

Abstract

Background: Hepatocellular carcinoma (HCC) associated with macroscopic vascular invasion and distant metastasis is an advanced-stage disease with an extremely poor prognosis and low survival rate. Therefore, there is an urgent need to develop novel therapeutic strategies to extend the lives of patients with advanced HCC.

Case presentation: We represent a case of HCC with macroscopic vascular invasion and pulmonary metastasis responding dramatically to the combination treatment with drug-eluting beads transarterial chemoembolization (DEB-TACE) and Huaier granule. A 64-year-old man with hepatitis B virus (HBV)-induced liver cirrhosis was diagnosed with advanced HCC involved renal vein and inferior vena cava accompanied by pulmonary metastasis. The patient received three cycles of on-demand DEB-TACE from 9th September 2016 to 22nd August 2017 and combined with Huaier granule 20 g three times a day orally. Eight months following the treatment, complete response occurred with regression of HCC and vascular thrombus and disappearance of pulmonary metastasis. The levels of AFP had decreased from 8165.8ng/mL to within the normal range (1.7 ng/mL). This is the first case report of complete response of HCC to the combination treatment with DEB-TACE and Huaier granule. At the most recent follow-up, he remained in remission 36 months after cessation of treatment without clinical or imaging evidence of disease recurrence. The current overall survival is 54 months since the initial treatment.

Conclusion: Data from this clinical case report suggest that the combination treatment with DEB-TACE and Huaier granule is a promising therapeutic option for advanced HCC with macroscopic vascular invasion and distant metastasis.

Keywords: Huaier; drug-eluting beads; hepatocellular carcinoma; traditional Chinese medicine; vascular invasion.

© 2021 Zhou et al.

Conflict of interest statement

The authors declare that they have no competing interests.

• Cited by 1 article
• 18 references
• 6 figures

Differential effects of Huaier aqueous extract on human CD4 ⁺ T lymphocytes from patients with primary immune thrombocytopenia

Exp Hematol. 2021 Sep;101-102:58-67. doi: 10.1016/j.exphem.2021.08.005. Epub 2021 Aug 24.　I F 3.084

Authors

Bo Yuan  ¹ , Chunlai Yin  ¹ , Xiaokang Ye  ¹ , Ziran Bai  ¹ , Zhimin Lu  ¹ , Xia Li  ¹ , Mahmoud Al-Azab  ¹ , Lijun Mu  ² , Weiping Li  ³

Affiliations

• ¹ Department of Immunology, Dalian Medical University, Dalian, Liaoning, China.
• ² Department of Hematology, Second Hospital of Dalian Medical University, Dalian, Liaoning, China. Electronic address: dlmulijun@163.com.
• ³ Department of Hematology, Second Hospital of Dalian Medical University, Dalian, Liaoning, China; Department of Immunology, Dalian Medical University, Dalian, Liaoning, China. Electronic address: liweiping0910@sina.com.
• PMID: 34450221
• DOI: 10.1016/j.exphem.2021.08.005

Abstract

Huaier, a traditional Chinese medicine, is currently used to treat certain types of cancer in the clinic and is also regarded as an immune-modulating and immune-enhancing agent that regulates immune cells. Emerging evidence indicates that an imbalance of immune cells, such as CD4⁺ T helper (Th) lymphocytes, contributes to the progression of immune thrombocytopenia (ITP), but the effects of Huaier on the regulation of CD4⁺ T cells are not yet fully elucidated. In the present study, Jurkat cells and peripheral blood mononuclear cells (PBMCs) from patients with ITP and healthy volunteers were treated with Huaier aqueous extract (HR). The CCK-8 assay revealed that HR suppressed the proliferation of Jurkat cells in a dose-dependent manner, whereas 3 mg/mL could decrease cell viability by 50%. At the latter concentration, the activation of CD4⁺ T cells from patients with ITP was partially attenuated. In addition, HR could correct the unbalanced Th1/Th2 polarization and inhibit the secretion of pro-inflammatory factors interleukin (IL)-2, tumor necrosis factor-α, and interferon-γ. It also suppressed Treg and facilitated Th17 differentiation, but did not change the levels of IL-10 and transforming growth factor-β. Thus, this study provides more information on how Huaier regulates cellular immunity and improves our understanding of the use of Huaier in ITP.

Copyright © 2021. Published by Elsevier Inc.

• Cited by 1 article

Huaier polysaccharides suppress triple-negative breast cancer metastasis and epithelial-mesenchymal transition by inducing autophagic degradation of Snail

Cell Biosci. 2021 Sep 4;11(1):170. doi: 10.1186/s13578-021-00682-6.　I F 6.068

Authors

Yuan Tian ^{#  1   2} , Jin Wu ^#  1 , Lingjuan Zeng ^#  1 , Linxi Zhou  ¹ , Ying Hu  ¹ , Qinwen Pan  ¹ , Wei Liu  ¹ , Yuzhao Yan  ¹ , Ziwei Wu  ¹ , Zhaoyu Wang  ¹ , Zhen Zeng  ¹ , Peng Tang  ³ , Jun Jiang  ⁴, Minghao Wang  ⁵

Affiliations

• ¹ Breast Disease Center, Southwest Hospital, Army Medical University, 30# Gaotanyan street, Chongqing, 400038, China.
• ² Department of General Surgery, Linyi People’s Hospital, Linyi, 276000, China.
• ³ Breast Disease Center, Southwest Hospital, Army Medical University, 30# Gaotanyan street, Chongqing, 400038, China. southwestbreast5@163.com.
• ⁴ Breast Disease Center, Southwest Hospital, Army Medical University, 30# Gaotanyan street, Chongqing, 400038, China. jcbd@medmail.com.cn.
• ⁵ Breast Disease Center, Southwest Hospital, Army Medical University, 30# Gaotanyan street, Chongqing, 400038, China. minghaowang_swh@163.com.

^# Contributed equally.

• PMID: 34481526
• PMCID: PMC8417980
• DOI: 10.1186/s13578-021-00682-6

Free PMC article

Abstract

Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and the targeted therapies are lacking for this type of cancer. We previously demonstrated that Huaier effectively improve 5-year OS and DFS in stage III TNBC patients, and the polysaccharides of Huaier (PS-T) have been identified as the major components of Huaier. However, the mechanisms of anti-tumor action of PS-T is unclear. This study aimed to investigate the effect of PS-T on TNBC cell invasion and migration.

Results: This study showed that PS-T inhibited cell invasion and migration both in vitro and in vivo by inducing autophagy to suppress epithelial-mesenchymal transition (EMT). Autophagy inhibitor LY294002 or knockdown of ATG5 suppressed the inhibitory effects of PS-T. In addition, as a key transcription factor controlling EMT initiation, Snail was found to be degraded by PS-T induced autophagy. In addition, overexpression of Snail reversed the inhibitory effects of PS-T. Furthermore, it was confirmed that the expression of Snail was inversely correlated with LC3 and associated with poor prognosis using immunohistochemistry and TCGA database analysis, respectively.

Conclusions: This study demonstrated that PS-T could inhibit EMT in breast cancer cells by inducing autophagy to degrade Snail protein, thus improving the prognosis of TNBC, offering potential treatment alternatives for TNBC patients.

Keywords: Huaier; In vitro; In vivo; Invasion; Metastasis; Triple-negative breast cancer.

© 2021. The Author(s).

Conflict of interest statement

The authors declare that they have no competing interests.

• Cited by 3 articles
• 42 references
• 6 figures

Trends of rapamycin in survival benefits of liver transplantation for hepatocellular carcinoma

World J Gastrointest Surg. 2021 Sep 27;13(9):953-966. doi: 10.4240/wjgs.v13.i9.953.　I F 5.742

Authors

Yang Zhao  ¹ , Yu Liu  ¹ , Lin Zhou  ¹ , Guo-Sheng Du  ² , Qiang He  ¹

Affiliations

• ¹ Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
• ² Department of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Beijing 100853, China. duguosheng309@126.com.
• PMID: 34621472
• PMCID: PMC8462078
• DOI: 10.4240/wjgs.v13.i9.953

Free PMC article

Abstract

The proportion of liver transplantation (LT) for hepatocellular carcinoma (HCC) has kept on increasing over the past years and account for 20%-40% of all LT. Post-transplant HCC recurrence is considered the most important factor affecting the long-term survival of patients. The use of different types of immunosuppressive agents after LT is closely associated with an increased risk for HCC recurrence. The most commonly used conventional immunosuppressive drugs include the calcineurin inhibitors tacrolimus (FK506) and mammalian target of rapamycin inhibitor rapamycin (RAPA). Compared with tacrolimus, RAPA may carry an advantage in survival benefit because of its anti-tumor effects. However, no sufficient evidence to date has proven that RAPA could increase long-term recurrence-free survival and its anti-tumor mechanism of combined therapy remains incompletely clear. In this review, we will focus on recent advances in clinical application experience and basic research results of RAPA in patients undergoing LT for HCC to further guide the clinical practice.

Keywords: Hepatocellular carcinoma; Huaier granule; Lenvatinib; Liver transplantation; Programmed death protein-1; Rapamycin.

©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.

Conflict of interest statement

Conflict-of-interest statement: The authors declare no conflict of interests for this article.

• Cited by 1 article
• 79 references
• 1 figure

Kampo Medicine for Intractable Brain and Neurological Diseases

Brain Nerve. 2021 Dec;73(12):1371-1376. doi: 10.11477/mf.1416201949.　I F 0.178

[Article in Japanese]

Author

Masanori Niimi  ¹

Affiliation

• ¹ Masanori Niimi Clinic.
• PMID: 34848575
• DOI: 10.11477/mf.1416201949

Abstract

In Japan, 147 types of oral Kampo extract products are covered by the public insurance system; however, to the best of our knowledge, there are no large-scale randomized clinical trials. Therefore, the level of evidence or these products is low compared with that for medicines that have been introduced as insurance reimbursement drugs through randomized clinical trials. However, when conventional western medical treatments have not been effective or when patients desire a more effective therapy, Kampo extract products are one of the treatment options. Kampo extract products involve the adding of crude drugs and comprise a multi-component system. Therefore, it may be effective for various symptoms. I recommend that specialists use these products as complementary alternative medicines. I also introduce the “Huaier extract granule,” which is an orally bioavailable traditional Chinese medicine composed of granules containing an aqueous extract of Trametes robiniophila Murr (Huaier), a mushroom found on hardwood tree trunks, with potential immune-regulating activity. Huaier has immunity enhancement activity, such as antineoplastic property, as well as immunity regulating activity against diseases, such as asthma, psoriasis, and immunoglobulin A nephritis. Therefore, for some intractable diseases, especially when the disease is thought to involve an immune disorder, Huaier can be an additional treatment option.

Huaier granule prevents the recurrence of early-stage hepatocellular carcinoma after thermal ablation: A cohort study

J Ethnopharmacol. 2021 Dec 5;281:114539. doi: 10.1016/j.jep.2021.114539. Epub 2021 Aug 21.　I F 4.36

Authors

Zhen Wang  ¹ , Xiao-Ling Yu  ² , Jing Zhang  ² , Zhi-Gang Cheng  ² , Zhi-Yu Han  ² , Fang-Yi Liu ² , Jian-Ping Dou  ² , Yi Kong  ³ , Xue-Juan Dong  ² , Qin-Xian Zhao  ² , Jie Yu  ⁴ , Ping Liang  ⁵, Wei-Zhong Tang  ⁶

Affiliations

• ¹ Department of Gastrointestinal Surgery, Affiliated Tumor Hospital, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, PR China; Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, 100853, China.
• ² Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, 100853, China.
• ³ Department of Clinical Laboratory Medicine, Chinese PLA General Hospital & Postgraduate Medical School, Beijing, 100853, China; Department of Clinical Laboratory Medicine, Jining First People’s Hospital, Jining, Shandong Province, 272000, PR China.
• ⁴ Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, 100853, China. Electronic address: yu-jie301@hotmail.com.
• ⁵ Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, 100853, China. Electronic address: liangping301@126.com.
• ⁶ Department of Gastrointestinal Surgery, Affiliated Tumor Hospital, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, PR China; Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, 530021, PR China. Electronic address: tangweizhong@gxmu.edu.cn.
• PMID: 34428522
• DOI: 10.1016/j.jep.2021.114539

Free article

Abstract

Ethnopharmacological relevance: Clinical trials have demonstrated that Trametes robinophila Murr (Huaier granule) can inhibit recurrence and metastasis after hepatocellular carcinoma (HCC) resection, but its efficacy as an adjuvant therapy after thermal ablation of early HCC is unknown.

Aim of the study: To analyze the prognostic value and side effects of Huaier granules in HCC patients undergoing thermal ablation.

Materials and methods: Clinical information from 340 eligible subjects with early-stage HCC who were admitted to our department from September 1, 2008 to January 1, 2019 was extracted from the electronic medical record database. They were divided into the thermal ablation + TCM group and the thermal ablation group. Differences in their overall survival (OS), progression-free survival (PFS), extrahepatic metastatic rate (EMR), and therapeutic side effects (TSEs) between the two groups were compared. Beneficiaries of the integrated treatment and adequate treatment length were predicted.

Results: The median follow-up was 32.5 months (range 2-122 months). The 1-year, 3-year and 5-year OS rates in the integrated treatment group and the control group were 93.2% vs. 92.6%, 54.5% vs. 51.4%, 23.5% vs. 19.7% (p = 0.110, HR 0.76(0.54-1.07)). The 1-year, 3-year and 5-year PFS rates were 78.8% vs. 69.4%, 50.6% vs. 40.6%, 35.3% vs. 26.5%, respectively (p = 0.020, HR 0.67(0.48-0.94)). The median OS (35 vs. 31 months) and PFS (24 vs. 12.5 months) were longer in the integrated treatment group. The EMR in the integrated treatment group was significantly lower than that in the control group (p = 0.018, HR 0.49 (0.27-0.89)). Patients with any two of the following three factors might be predicted to be beneficiaries of the integrated treatment, including younger than 65 years (p =0.039, HR 0.70 (0.50-0.98)), single tumor (p = 0.035, HR 0.70 (0.50-0.98), and tumor size ≤3 cm (p = 0.029, HR 0.69 (0.50-0.96). Patients with continuous oral administration of TCM following ablation had a lower probability of recurrence and metastasis within 2 years (p = 0.015, HR 0.67 (0.49-0.93)). Although the integrated treatment group reported a higher incidence of nausea and emesis, there were no significant differences between the two groups.

Conclusion: TCM following ablation may prolong PFS and suppress recurrence in patients with HCC, with continuous oral administration for more than 2 years maybe experience a greater benefit. The TSEs of the treatment are mild and can be tolerated.

Keywords: Hepatocellular carcinoma; Metastasis; Recurrence; Thermal ablation; Traditional Chinese medicine.

Copyright © 2021 Department of Gastrointestinal Surgery, Affiliated Tumor Hospital, Guangxi Medical University. Published by Elsevier B.V. All rights reserved.

• Cited by 7 articles 

Efficacy and Safety of Huaier Granule as an Adjuvant Therapy for Cancer: An Overview of Systematic Reviews and Meta-Analyses

Integr Cancer Ther. 2022 Jan-Dec;21:15347354221083910. doi: 10.1177/15347354221083910.　I F 3.279

Authors

Jixin Chen  ^1   2 , Shuqi Chen  ³ , Yushu Zhou  ² , Sumei Wang  ² , Wanyin Wu  ²

Affiliations

• ¹ The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
• ² Department of Oncology, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangdong-HongKong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
• ³ Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
• PMID: 35245981
• PMCID: PMC8902013
• DOI: 10.1177/15347354221083910

Free PMC article

Abstract

Introduction: In China, Huaier granule (HG) is widely applied to tumor adjuvant therapy. However, systematic reviews (SRs) or meta-analyses (MAs) published continuously failed to reach a consensus, without convincing evidence. An overview should be conducted to summarize the evidence-based progress and try to provide some value references for relative research and clinical practice in the future.

Methods: From inception to October 2021, 8 databases in English and Chinese were searched. SRs/MAs meeting the inclusion and exclusion criteria were included. Relevant criteria were used to evaluate SRs/MAs including methodological quality, reporting quality, risk of bias, and evidence quality of effect and safety.

Results: The short-term effect, long-term effect, and safety in 6 included SRs/MAs were assessed in this overview according to quantitative synthesis. Results assessed by AMSTAR-2, PRISMA, and ROBIS were generally unsatisfactory with the main problems on registration or protocol, a search of grey literature, a list of excluded studies, bias of each synthetic result, and inadequate report of search strategy and synthesis methods. Additionally, 28 items were assessed as moderate quality while 12 items were low-quality and 6 items were very low-quality in GRADE. Risk of bias was the main downgrading factor.

Conclusion: HG may be a promising adjuvant therapy for cancer. However, high-quality SRs/MAs and RCTs should be conducted to provide sufficient evidence so as to draw a definitive conclusion.

Keywords: Huaier granule; TCM; adjuvant therapy; cancer; overview.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

• 35 references
• 5 figures

Polysaccharides Produced by the Mushroom Trametes robiniophila Murr Boosts the Sensitivity of Hepatoma Cells to Oxaliplatin via the miR-224-5p/ABCB1/P-gp Axis

Integr Cancer Ther. 2022 Jan-Dec;21:15347354221090221. doi: 10.1177/15347354221090221.　 I F 3.279

Authors

Yudong Gou  ¹ , Xia Zheng  ¹ , Wenming Li  ² , Hongyu Deng  ³ , Shukui Qin  ^1   2

Affiliations

• ¹ Nanjing University of Chinese Medicine, Nanjing, China.
• ² Nanjing Jinling Hospital: East Region Military Command General Hospital, Nanjing, China.
• ³ Guangzhou University of Chinese Medicine, Guangzhou, China.
• PMID: 35426328
• PMCID: PMC9014716
• DOI: 10.1177/15347354221090221

Free PMC article

Abstract

Aim: To investigate the mechanisms employed by PS-T (polysaccharides of Trametes, PS-T), the main active ingredient of Huaier granules, to improve the susceptibility of hepatoma cells to oxaliplatin (OXA).

Methods: Cell proliferation in response to PS-T was determined both in vitro and in vivo. The effects of PS-T on miRNAs were analyzed with the use of a microarray. MiRNAs were screened under specific conditions (P < .05, log_FoldChange > ABS [1.5]) and further silenced or overexpressed by liposome transfection. Levels of ABCB1 mRNA and P-gp were detected by qRT-PCR and western blot analysis, respectively. A dual fluorescence assay was performed to determine whether miRNA directly targets ABCB1.

Results: PS-T enhanced the inhibitory effect of OXA in human hepatoma cells and xenografts. Among 5 up-regulated miRNAs, overexpression of only miR-224-5p inhibited the expression of ABCB1 mRNA and P-gp, while silencing of miR-224-5p had an opposite effect. Moreover, miR-224-5p can directly target the 3′-UTR of ABCB1.

Conclusion: PS-T increases the sensitivity of human hepatoma cells to OXA via the miR-224-5p/ABCB1/P-gp axis.

Keywords: Trametes robiniophila Murr; chemotherapy resistance; hepatocellular carcinoma; miR-224-5p; microRNA array.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

• 39 references
• 5 figures

GPR30 Activation Promotes the Progression of Gastric Cancer and Plays a Significant Role in the Anti-GC Effect of Huaier

J Oncol. 2022 Jan 19;2022:2410530. doi: 10.1155/2022/2410530. eCollection 2022.　I F 4.375

Authors

Xiao-Feng Wang  ^1   2 , Can Hu  ^1   3 , Shao-Wei Mo  ¹ , Jing-Li Xu  ¹ , Yan Liu  ¹ , Han-Dong Xu  ¹, Li Yuan  ³ , Ling Huang  ³ , Jian-Fa Yu  ³ , Xiang-Dong Cheng  ^3   4 , Zhi-Yuan Xu  ^3   4

Affiliations

• ¹ Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.
• ² Affiliated Cixi Hospital, Wenzhou Medical University (Cixi People’s Hospital), Ningbo 315300, China.
• ³ The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China.
• ⁴ Diagnosis and Therapy Center of Upper Gastrointestinal Tumor in Zhejiang Province, Hangzhou 310022, China.
• PMID: 35096058
• PMCID: PMC8791733
• DOI: 10.1155/2022/2410530

Free PMC article

Abstract

Gastric cancer (GC) is one of the most common types of cancer. The n-butanol extract of Huaier (NEH) is the alcohol-soluble part extracted by the systematic solvent method, which is effective against gastric cancer (GC). However, the mechanism of action of NEH remains unclear. In this study, we aim to evaluate the clinical relevance of GPR30 expression in GC patients and the role of the GPR30/PI3K/AKT signalling pathway in the anti-GC effect of NEH. The expression of GPR30 was examined using immunohistochemistry. Cell counting kit 8 (CCK-8) assay, wound healing, and transwell experiments were used to investigate the viability, migration, and invasion of gastric cancer cells. Western blotting was used to detect the expression of GPR30 and its downstream signalling molecules of the PI3K/AKT signalling pathway. Gastric cancer patient-derived xenografts (PDX) mouse model was used to evaluate the antitumor effect of NEH in vivo. In addition, the graded doses and the maximum tolerated dose of NEH were administered intraperitoneally into the mice for acute toxicity test. We demonstrate that GPR30 expression in GC tissues was significantly higher than that in corresponding adjacent noncancerous tissues and the expression of GPR30 was correlated with a poor prognosis in GC patients. Moreover, GPR30 expression was involved in the migration and invasion of GC cells in vitro. Additionally, we found that NEH can suppress the growth of GC in patient-derived xenograft tumors in vivo. Furthermore, NEH inhibited the proliferation, migration, and invasion in GC cells in a concentration-dependent manner through inhibiting the GPR30-mediated PI3K/AKT signalling pathway in vitro. Acute toxicity test showed that NEH caused no toxic reaction or death and the maximum tolerated dose of NEH in mice was greater than 1600 mg/kg. Our results demonstrate that the high expression of GPR30 is an independent factor of poor prognosis in patients with GC and NEH could be a new agent for the treatment of gastric cancer.

Copyright © 2022 Xiao-feng Wang et al.

Conflict of interest statement

The authors declare that they have no conflicts of interest.

• 24 references
• 7 figures

Trametes robiniophila represses angiogenesis and tumor growth of lung cancer via strengthening let-7d-5p and targeting NAP1L1

Bioengineered. 2022 Mar;13(3):6698-6710. doi: 10.1080/21655979.2021.2012619.　I F 3.269

Authors

HuiZhu Gan  ¹ , XinXin Xu  ¹ , YinYin Bai  ¹

Affiliation

• ¹ Department of Hematology and Oncology, China-Japan Union Hospital of Jilin University, Changchun City, JiLin Province, China.
• PMID: 34898380
• PMCID: PMC8973683
• DOI: 10.1080/21655979.2021.2012619

Free PMC article

Abstract

Trametes robiniophila (Huaier) is available to refrain lung cancer (LC) cell progression, but its impact and mechanism on angiogenesis of LC are not proved. The study was to explore the potential mechanism of Huaier repressing angiogenesis and tumor growth in LC via strengthening let-7d-5p and targeting NAP1L1. Let-7d-5p and NAP1L1 expression was detected in LC tissues and cells (A549). Pretreatment of A549 cells was with Huaier. Transfection of changed let-7d-5p and NAP1L1 was to A549 cells to uncover their roles in LC cell progression with angiogenesis. Evaluation of the impact of let-7d-5p on angiogenesis in LC was in vitro in a mouse xenograft model. Identification of the targeting of let-7d-5p with NAP1L1 was clarified. The results clarified reduced let-7d-5p but elevated NAP1L1 were manifested in LC. Huaier restrained angiogenesis and tumor growth of LC in vivo and in vitro; Augmented let-7d-5p or declined NAP1L1 motivated the therapy of Huaier on LC; Let-7d-5p negatively modulated NAP1L1; Elevated NAP1L1 reversed the influence of enhancive let-7d-5p. These results strongly suggest that Huaier represses angiogenesis and tumor growth in LC via strengthening let-7d-5p and targeting NAP1L1. Huaier/let-7d-5p/NAP1L1 axis is supposed to be a promising target for the treatment of angiogenesis and tumor growth in LC via elevated let-7d-5p and targeted NAP1L1.

Keywords: NAP1L1; Trametes robiniophila; angiogenesis; let-7d-5p; lung cancer.

Conflict of interest statement

No potential conflict of interest was reported by the author(s).

• Cited by 4 articles
• 48 references
• 5 figures

Epigenetics of Triple-Negative Breast Cancer via Natural Compounds

Curr Med Chem. 2022 Mar 4;29(8):1436-1458. doi: 10.2174/0929867328666210707165530.　I F 4.53

Authors

Mohammed Kaleem  ¹ , Maryam Perwaiz  ² , Suza Mohammad Nur  ¹ , Abdulrasheed O Abdulrahman  ¹ , Wasim Ahmad  ³ , Fahad A Al-Abbasi  ¹ , Vikas Kumar  ⁴ , Mohammad Amjad Kamal  ⁵ , Firoz Anwar  ¹

Affiliations

• ¹ Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
• ² Department of Sciences, University of Toronto, Mississauga, Canada.
• ³ Department of Kuliyate Tib, National Institute of Unani Medicine, Kottigepalya, Bengaluru, India- 560091.
• ⁴ Natural Product Discovery Laboratory, Department of Pharmaceutical Sciences, Shalom Institute of Health and Allied Sciences. SHUATS, Naini, Prayagraj, India.
• ⁵ West China School of Nursing / Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
• PMID: 34238140
• DOI: 10.2174/0929867328666210707165530

Abstract

Triple-negative breast cancer (TNBC) is a highly resistant, lethal, and metastatic sub-division of breast carcinoma, characterized by the deficiency of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). In women, TNBC shows a higher aggressive behavior with poor patient prognosis and a higher recurrence rate during reproductive age. TNBC is defined by the presence of epithelial- to-mesenchymal-transition (EMT), which shows a significant role in cancer progression. At the epigenetic level, TNBC is characterized by epigenetic signatures, such as DNA methylation, histone remodeling, and a host of miRNA, MiR-193, LncRNA, HIF- 2α, eEF2K, LIN9/NEK2, IMP3, LISCH7/TGF-β1, GD3s, KLK12, mediated regulation. These modifications either are silenced or activate the necessary genes that are prevalent in TNBC. The review is based on epigenetic mediated mechanistic changes in TNBC. Furthermore, Thymoquinone (TQ), Regorafenib, Fangjihuangqi decoction, Saikosaponin A, and Huaier, etc., are potent antitumor natural compounds extensively reported in the literature. Further, the review emphasizes the role of these natural compounds in TNBC and their possible epigenetic targets, which can be utilized as a potential therapeutic strategy in the treatment of TNBC.

Keywords: DNA methylation; TNBC; breast cancer; estrogen receptor; genes; natural compounds.

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

• Cited by 1 article

Sarcomatoid intrahepatic cholangiocarcinoma with good patient prognosis after treatment with Huaier granules following hepatectomy: A case report

World J Clin Cases. 2022 Mar 26;10(9):2829-2835. doi: 10.12998/wjcc.v10.i9.2829.　I F 1.337

Authors

Ji-Ye Feng  ¹ , Xian-Peng Li  ² , Zong-Yang Wu  ¹ , Li-Ping Ying  ¹ , Chang Xin  ¹ , Zhen-Zhen Dai  ³ , Yao Shen  ⁴ , Yi-Feng Wu  ⁵

Affiliations

• ¹ Department of Hepatobiliary & Pancreas Surgery, The Affiliated People’s Hospital of Ningbo University, Ningbo 315040, Zhejiang Province, China.
• ² Department of Infectious Disease, The Affiliated People’s Hospital of Ningbo University, Ningbo 315040, Zhejiang Province, China.
• ³ Department of Pathology, The Affiliated People’s Hospital of Ningbo University, Ningbo 315040, Zhejiang Province, China.
• ⁴ Department of Radiology, The Affiliated People’s Hospital of Ningbo University, Ningbo 315040, Zhejiang Province, China.
• ⁵ Department of Hepatobiliary & Pancreas Surgery, The Affiliated People’s Hospital of Ningbo University, Ningbo 315040, Zhejiang Province, China. wyf5495@163.com.
• PMID: 35434085
• PMCID: PMC8968806
• DOI: 10.12998/wjcc.v10.i9.2829

Free PMC article

Abstract

Background: Sarcomatoid intrahepatic cholangiocarcinoma (SICC) is an extremely rare and highly invasive malignant tumor of the liver. The precise pathologic mechanism of SICC has not been clearly identified, and the prognosis is very poor. The effectiveness of the treatment strategy of radical hepatectomy combined with Huaier granules has not yet been reported.

Case summary: The patient was a 69-year-old male who presented with intermittent right upper abdominal pain for one month and 4-pound weight loss before admission. Abdominal magnetic resonance imaging and magnetic resonance cholangiopancreatography showed multiple stones in the bile ducts accompanied by dilatation of the intrahepatic and extrahepatic bile ducts. The preoperative diagnoses were right intrahepatic bile duct stones and extrahepatic bile duct stones; thus, surgical resection was performed. Choledochoscopy showed that the bile duct wall of the right anterior lobe was thickened, and a mass was visible in the duct. Then, a biopsy was performed, and rapid frozen-section biopsy analysis indicated that the tumor was malignant. The final diagnosis was SICC (T1aN0M0). Huaier granules were taken by the patient as anticancer therapy after surgery. The patient attended follow-up for 72 mo with no tumor recurrence or metastasis.

Conclusion: Sarcomatous intrahepatic cholangiocarcinoma is an extremely rare, aggressive malignancy, and the diagnostic gold standard is pathological diagnosis. We reported the first case of successful treatment with Huaier granules as anticancer therapy after surgery, which indicated that Huaier granules are safe and effective. Further studies are needed to study the anticancer molecular mechanisms of Huaier granules in sarcomatous intrahepatic cholangiocarcinoma.

Keywords: Case report; Diagnose; Hepatectomy; Huaier granules; Sarcomatous intrahepatic cholangiocarcinoma; Therapy.

©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.

Conflict of interest statement

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

• 15 references
• 2 figures

Huaier attenuates the adverse effects of pyroptosis by regulating the methylation of rat mesangial cells: an in vitro study

BMC Complement Med Ther. 2022 Mar 29;22(1):92. doi: 10.1186/s12906-022-03559-4.　I F 3.659

Authors

Wenjia Geng ^#  1 , Can Tu ^{#  2   3} , Dahao Chen ^#  2 , Zhaoyu Lu  ^{2   4   5} , Wei Mao  ^{6   7   8} , Hanyu Zhu  ⁹

Affiliations

• ¹ Peking University People’s Hospital, Beijing, China.
• ² The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
• ³ Department of nephrology, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan, China.
• ⁴ State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangzhou, China.
• ⁵ Department of nephrology, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Yuexiu District, Guangzhou, Guangdong province, China.
• ⁶ The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. maowei@gzucm.edu.cn.
• ⁷ State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangzhou, China. maowei@gzucm.edu.cn.
• ⁸ Department of nephrology, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Yuexiu District, Guangzhou, Guangdong province, China. maowei@gzucm.edu.cn.
• ⁹ Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, No.28 Fuxing Road, Haidian District, Beijing, China. hanyuzhu301@126.com.

^# Contributed equally.

• PMID: 35351070
• PMCID: PMC8966145
• DOI: 10.1186/s12906-022-03559-4

Free PMC article

Abstract

Background: Pyroptosis is a highly programmed inflammatory cell death process that represents an innate immune response. In this study, the occurrence of pyroptosis in rat mesangial cells (RMCs) and the effect of Huaier (Trametes robiniophia Murr) on this process were investigated.

Methods: RMCs were incubated with OX7 antibodies (0.5 μg/ml, 2.5 μg/ml, 10 μg/ml), normal rat serum (NRS) and Huaier (1 mg/ml, 5 mg/ml, 10 mg/ml). RMC morphology was observed under a light microscope and by immunofluorescence. Lactate dehydrogenase (LDH) release was assessed using the CytoTox 96 Non-Radioactive Cytotoxicity Assay Kit. Western blot assays were performed, and then the RMCs were incubated with the methylase DNMT3B and the demethylase 5-aza-2′-deoxycytidine.

Results: Morphological, LDH, immunofluorescence and western blot analyses showed that RMCs were lysed when stimulated with OX7 antibodies and NRS. RMC lysis released inflammatory cytokines (interleukin-18, interleukin-1β, monocyte chemoattractant protein-1 and intracellular adhesion molecule-1), and Huaier protected RMCs by controlling lysis and the levels of inflammatory cytokines. Lysis was mediated by pyroptosis due to the positive expression of GSDME. The methylase DNMT3B reduced the expression of GSDME induced by OX7 together with NRS. Furthermore, Huaier significantly suppressed the expression of GSDME, which was increased by 5-aza-2′-deoxycytidine.

Conclusions: Pyroptosis might occur in RMCs, and Huaier can protect RMCs by upregulating the methylation of a group of molecules.

Keywords: GSDME; Huaier; Methylation; Pyroptosis; Rat mesangial cells.

© 2022. The Author(s).

Conflict of interest statement

The authors have no conflicts of interest to declare.

• 37 references
• 9 figures

Huaier Polysaccharide Interrupts PRV Infection via Reducing Virus Adsorption and Entry

Viruses. 2022 Apr 1;14(4):745. doi: 10.3390/v14040745.　I F 4.911

Authors

Changchao Huan  ^{1   2   3} , Jingting Yao  ^{1   2   3} , Weiyin Xu  ^{1   2   3} , Wei Zhang  ^{1   2   3} , Ziyan Zhou  ^{1   2   3} , Haochun Pan  ^{1   2   3} , Song Gao  ^{1   2   3}

Affiliations

• ¹ Institutes of Agricultural Science and Technology Development, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
• ² Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
• ³ Key Laboratory of Avian Bioproduct Development, Ministry of Agriculture and Rural Affairs, Yangzhou 225009, China.
• PMID: 35458475
• PMCID: PMC9026689
• DOI: 10.3390/v14040745

Free PMC article

Abstract

A pseudorabies virus (PRV) novel virulent variant outbreak occurred in China in 2011. However, little is known about PRV prevention and treatment. Huaier polysaccharide has been used to treat some solid cancers, although its antiviral activity has not been reported. Our study confirmed that the polysaccharide can effectively inhibit infection of PRV XJ5 in PK15 cells. It acted in a dose-dependent manner when blocking virus adsorption and entry into PK15 cells. Moreover, it suppressed PRV replication in PK15 cells. In addition, the results suggest that Huaier polysaccharide plays a role in treating PRV XJ5 infection by directly inactivating PRV XJ5. In conclusion, Huaier polysaccharide might be a novel therapeutic agent for preventing and controlling PRV infection.

Keywords: Huaier polysaccharide; antiviral; infection; pseudorabies virus.

Conflict of interest statement

The authors declare no conflict of interest.

• 44 references
• 7 figures

An extraction from Trametes robiniophila Murr. ( Huaier) inhibits non-small cell lung cancer proliferation via targeting to epidermal growth factor receptor

Bioengineered. 2022 Apr;13(4):10931-10943. doi: 10.1080/21655979.2022.2066757.　I F 3.269

Authors

Fei Lv  ¹ , Xiaoqi Li  ² , Ying Wang  ¹

Affiliations

• ¹ Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
• ² Third Department of Oncology, The People’s Hospital of Liaoning Province.
• PMID: 35470770
• PMCID: PMC9162005
• DOI: 10.1080/21655979.2022.2066757

Free PMC article

Abstract

An extraction from Trametes robiniophila Murr. (Huaier) is a kind of natural fungus growing from the sophora japonica tree. Huaier is widely applied to cure the hepatocellular cancer (HCC). However, the medicinal fungus’ curative result on non-small-cell lung cancer (NSCLC) is not well elaborated. In this study, we applied in vitro experiments to study Huaier’s curative result on NSCLC. The potential Huaier targets were predicted using bioinformatics and validated by western blotting. We further elucidated the mechanism of Huaier targeting by molecular docking, kinase activity assay, CEllular Thermal Shift Assays (CETSAs). At last, in vivo curative result was verified further. Huaier weakened proliferation and promoted apoptosis of the NSCLC cell lines. According to bioinformatics, Epidermal Growth Factor Receptor (EGFR) may be the target of Huaier. Western blotting showed that Huaier can attenuate the activation of EGFR and we found that Huaier can dock to EGFR. Huaiersignificantly inhibited the tumor growth by weakening the expression of p-EGFR in vivo. This study offers a new idea for further understanding of Huaier and shows its potential as a therapeutic agent.

Keywords: Molecular docking simulation; carcinoma; non-small-cell lung; traditional Chinese medicine.

Conflict of interest statement

No potential conflict of interest was reported by the author(s).

• 38 references
• 7 figures

Chinese Herbal Medicine for Primary Liver Cancer Therapy: Perspectives and Challenges

Front Pharmacol. 2022 May 5;13:889799. doi: 10.3389/fphar.2022.889799. eCollection 2022.　I F 5.81

Authors

Kexin Li  ^1   2 , Kunmin Xiao  ^1   3 , Shijie Zhu  ³ , Yong Wang  ⁴ , Wei Wang  ^{1   5   6}

Affiliations

• ¹ Graduate School, Beijing University of Chinese Medicine, Beijing, China.
• ² Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing, China.
• ³ Department of Oncology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
• ⁴ School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
• ⁵ Institute of Prescription and Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, China.
• ⁶ Guangdong Provinvial Key Laboratory of TCM Pathogenesis and Prescriptions of Heart and Spleen Diseases, Guangzhou, China.
• PMID: 35600861
• PMCID: PMC9117702
• DOI: 10.3389/fphar.2022.889799

Free PMC article

Abstract

Primary liver cancer (PLC) is one of the most common solid malignancies. However, PLC drug development has been slow, and first-line treatments are still needed; thus, studies exploring and developing alternative strategies for effective PLC treatment are urgently needed. Chinese herbal medicine (CHM) has long been applied in the clinic due to its advantages of low toxicity and targeting of multiple factors and pathways, and it has great potential for the development of novel natural drugs against PLC. Purpose: This review aims to provide an update on the pharmacological mechanisms of Chinese patent medicines (CPMs) and the latest CHM-derived compounds for the treatment of PLC and relevant clinical evaluations. Materials and Methods: A systematic search of English literature databases, Chinese literature, the Clinical Trials Registry Platform, and the Chinese Clinical Trial Registry for studies of CHMs for PLC treatment was performed. Results: In this review, we summarize the clinical trials and mechanisms of CPMs for PLC treatment that have entered the clinic with the approval of the Chinese medicine regulatory authority. These CPMs included Huaier granules, Ganfule granules, Fufang Banmao capsules, Jinlong capsules, Brucea javanica oil emulsions, and compound kushen injections. We also summarize the latest in vivo, in vitro, and clinical studies of CHM-derived compounds against PLC: icaritin and ginsenoside Rg3. Dilemmas facing the development of CHMs, such as drug toxicity and low oral availability, and future developments are also discussed. Conclusion: This review provides a deeper the understanding of CHMs as PLC treatments and provides ideas for the development of new natural drugs against PLC.

Keywords: Chinese herbal medicines; Chinese patent medicine; clinical trials; pharmacological mechanisms; primary liver cancer.

Copyright © 2022 Li, Xiao, Zhu, Wang and Wang.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

• 140 references
• 1 figure

Metabolomic comparison between natural Huaier and artificial cultured Huaier

Biomed Chromatogr. 2022 Jun;36(6):e5355. doi: 10.1002/bmc.5355. Epub 2022 Feb 25.　I F　1.902

Authors

Tongtong Jian  ¹ , Yu Zhang  ¹ , Guoying Zhang  ¹ , Jianya Ling  ^1   2

Affiliations

• ¹ School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.
• ² State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China.
• PMID: 35156219
• DOI: 10.1002/bmc.5355

Abstract

Vanderbylia robiniophila (Murrill) B.K. (Huaier) is a kind of higher fungal fruiting body that is parasitic on the trunk of Sophora japonica and Robinia pseudoacacia L.. As a traditional Chinese medicine with a history of more than 1,600 years, Huaier has attracted wide attention for its excellent anticancer activity. A systematic study on the metabolome differences between natural Huaier and artificial cultured Huaier was conducted using liquid chromatography-mass spectrometry in this study. Principal component analysis and orthogonal projection on latent structure-discriminant analysis results showed that cultured Huaier evidently separated and individually separated from natural Huaier, indicating metabolome differences between natural and cultured Huaier. Hierarchical clustering analysis was further performed to cluster the differential metabolites and samples based on their metabolic similarity. The higher contents of amino acids, alkaloids and terpenoids in natural Huaier make it an excellent choice as a traditional Chinese medicine for anticancer or nutritional supplementation. The results of the Bel-7,402 and A549 cell cytotoxicity tests showed that the anticancer activity of natural Huaier was better than that of cultured Huaier. This may be due to the difference in chemical composition, which makes the anticancer activities of natural and cultured Huaier different.

Keywords: Huaier; LC-MS; Metabolomics.

© 2022 John Wiley & Sons, Ltd.

• Cited by 1 article
• 53 references

Huaier Inhibits Gastric Cancer Growth and Hepatic Metastasis by Reducing Syntenin Expression and STAT3 Phosphorylation

J Oncol. 2022 Jun 15;2022:6065516. doi: 10.1155/2022/6065516. eCollection 2022.　I F 4.375

Authors

Yunfu Shi  ^1   2 , Li Yuan  ^{3   4   5} , Jingli Xu  ² , Handong Xu  ² , Lijing Wang  ³ , Ling Huang  ³, Zhiyuan Xu  ^{3   4   5} , Xiangdong Cheng  ^{3   4   5}

Affiliations

• ¹ Tongde Hospital Affiliated to Zhejiang Chinese Medical University (Tongde Hospital of Zhejiang Province), Hangzhou 310012, China.
• ² The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.
• ³ The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China.
• ⁴ Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou 310022, China.
• ⁵ Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, China.
• PMID: 35756080
• PMCID: PMC9217535
• DOI: 10.1155/2022/6065516

Free PMC article

Abstract

Gastric cancer (GC) is a common malignant tumor worldwide and poses a serious threat to human health. As a traditional Chinese medicine, Huaier (Trametes robiniophila Murr.) has been used in the clinical treatment of GC. However, the mechanism underlying the anticancer effect of Huaier remains poorly understood. In this study, we used in vivo imaging technology to determine the anticancer effect of the Huaier n-butanol extract (HBE) on orthotopic and hepatic metastasis of GC mouse models. We found that HBE suppressed tumor growth and metastasis without causing apparent host toxicity. Proteomic analysis of GC cells before and after HBE intervention revealed syntenin to be one of the most significantly downregulated proteins after HBE intervention. We further demonstrated that HBE suppressed the growth and metastasis of GC by reducing the expression of syntenin and the phosphorylation of STAT3 at Y705 and reversing the epithelial-mesenchymal transition (EMT). In addition, we confirmed that syntenin was highly expressed in GC tissue and correlated with metastasis and poor prognosis. In conclusion, our results suggest that Huaier, a clinically used anticancer drug, may inhibit the growth and liver metastasis of GC by inhibiting the syntenin/STAT3 signaling pathway and reversing EMT.

Copyright © 2022 Yunfu Shi et al.

Conflict of interest statement

The authors declare that they have no conflicts of interest.

• 37 references
• 8 figures

Huaier Induces Immunogenic Cell Death ViaCircCLASP1/PKR/eIF2α Signaling Pathway in Triple Negative Breast Cancer

Front Cell Dev Biol. 2022 Jun 16;10:913824. doi: 10.3389/fcell.2022.913824. eCollection 2022.　I F 6.684

Authors

Chen Li  ¹ , Xiaolong Wang  ¹ , Tong Chen  ¹ , Wenhao Li  ¹ , Xianyong Zhou  ¹ , Lishui Wang  ², Qifeng Yang  ^{1   3   4}

Affiliations

• ¹ Department of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
• ² Department of Clinical Laboratory, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
• ³ Department of Pathology Tissue Bank, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
• ⁴ Research Institute of Breast Cancer, Shandong University, Jinan, China.
• PMID: 35784473
• PMCID: PMC9243662
• DOI: 10.3389/fcell.2022.913824

Free PMC article

Abstract

Triple-negative breast cancer (TNBC) is the most lethal breast cancer subtype owing to the lack of targeted therapeutic strategies. Immunogenic cell death (ICD), a modality of regulated cancer cell death, offered a novel option for TNBC via augmenting tumor immunogenic microenvironment. However, few ICD-inducing agents are currently available. Here, we showed that Trametes robiniophila Murr (Huaier) triggered ICD in TNBC cells by promoting cell surface calreticulin (CRT) exposure, and increasing release of adenosine triphosphate (ATP) and high-mobility group protein B1 (HMGB1). Co-culturing with Huaier-treated TNBC cells efficiently enhanced the maturation of dendritic cells (DCs), which was further validated via cell-based vaccination assay. In the xenograft mouse model, oral administration of Huaier led to tumor-infiltrating lymphocytes (TILs) accumulation and significantly delayed tumor growth. Besides, depletion of endogenous T cells obviously abrogated the effect. Mechanically, Huaier could elicit endoplasmic reticulum (ER) stress-associated ICD through eIF2α signaling pathway. Further studies revealed that circCLASP1 was involved in the Huaier-induced immunogenicity by binding with PKR in the cytoplasm and thus blocking its degradation. Taken together, we highlighted an essential role of circCLASP1/PKR/eIF2α axis in Huaier-induced ICD. The findings of our study carried significant translational potential that Huaier might serve as a promising option to achieve long-term tumor remission in patients with TNBC.

Keywords: Huaier; ICD; PKR; circRNA; er stress.

Copyright © 2022 Li, Wang, Chen, Li, Zhou, Wang and Yang.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

• 54 references
• 7 figures

Complete response after combined chemoembolization and Huaier therapy for pulmonary metastasis of hepatocellular carcinoma: A case report

Asian J Surg. 2022 Aug;45(8):1589-1590. doi: 10.1016/j.asjsur.2022.03.035. Epub 2022 Mar 23.　I F 2.767

Authors

Renbiao Chen  ¹ , Pierre Umba Mabombo  ¹ , Hongjie Hu  ² , Yue Qian  ³

Affiliations

• ¹ Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, East Qingchun Road, Hangzhou, Zhejiang, 310016, PR China.
• ² Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, East Qingchun Road, Hangzhou, Zhejiang, 310016, PR China. Electronic address: Hongjiehu@zju.edu.cn.
• ³ Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, East Qingchun Road, Hangzhou, Zhejiang, 310016, PR China. Electronic address: qianyue2005@163.com.
• PMID: 35337720
• DOI: 10.1016/j.asjsur.2022.03.035

Free article

No abstract available

The treatment effects of Trametes Robiniophila Murr against colorectal cancer: A mini-review

Front Med (Lausanne). 2022 Aug 3;9:981516. doi: 10.3389/fmed.2022.981516. eCollection 2022.　I F 4.468

Authors

Bo Li  ¹ , Qian Cao  ² , Zhuo Liu  ³

Affiliations

• ¹ Department of Rehabilitation Medicine, China-Japan Union Hospital of Jilin University, Changchun, China.
• ² Department of Education, Jilin University Second Hospital, Changchun, China.
• ³ Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
• PMID: 35991644
• PMCID: PMC9381862
• DOI: 10.3389/fmed.2022.981516

Free PMC article

Abstract

Colorectal cancer (CRC) is a worldwide disease threatening people’s lives. Surgery and chemotherapy are still the main methods for CRC treatment. However, the side effects and chemotherapeutic drug resistance restrict the application of chemotherapy. Trametes Robiniophila Murr, also known as Huaier, is a traditional Chinese medicine that has been used for more than 1,600 years. Huaier extracts have promising anti-cancer effects on hepatoma, breast cancer, and gastric cancer. Nowadays, the tumor inhibition of Huaier on CRC has attracted more and more attention. This review mainly provides the possible anti-tumor mechanisms of Huaier for CRC treatment in apoptosis and inhibiting proliferation of tumor cells, preventing epithelial-mesenchymal transformation (EMT), weakening proliferation and differentiation of CRC stem cells, decreasing the vessel density in tumor tissues, and enhancing the immune system and chemotherapeutic efficacy. Huaier extract may be a good candidate for CRC treatment, especially when combined with other chemotherapeutic agents.

Keywords: Huaier; Trametes Robiniophila Murr; anticancer; colorectal cancer; mechanisms.

Copyright © 2022 Li, Cao and Liu.

Conflict of interest statement

The authors declare that this study received funding from Qidong Gaitianli Pharmaceutical Co., LTD. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.

• 46 references
• 1 figure