Mechanism of action of Huaier granules in treatment of hepatocellular carcinoma and advances in its clinical application / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) is the second leading cause of disease-related death in China and greatly threatens the health of residents. Recent studies have shown that traditional Chinese medicine plays an important role in the comprehensive treatment of HCC. Huaier granules have been recommended for the treatment of HCC, and its mechanism of action includes inhibiting angiogenesis, inhibiting the proliferation of HCC cells, inhibiting invasion and metastasis, inducing cell apoptosis, and regulating immune function. This article summarizes the research advances in the anti-HCC mechanism of Huaier granules and its application in clinical practice, in order to provide a reference for subsequent research and clinical treatment.

Huaier Granule for Breast Cancer Treatment / 日本補完代替医療学会誌

Huaier granule, which is clinically used in Japan as a health food, is originally a traditional Chinese medicine for immune dysfunction, such as cancer, in China. Huaier guanule emerged with abundant evidence, and is being prescribed to hepatocellular carcinoma, breast cancer, lung cancer, gastric cancer, et al. as indications in China. This review focused on the clinical evidence of Huaier guanule associated to breast cancer.

Systematic evaluation of Huaier Granules adjuvant treatment of primary liver cancer / 中国中药杂志

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.

Effect of Huaier aqueous extract on growth and metastasis of human non-small cell lung cancer NCI-H1299 cells and its underlying mechanisms / 中国中药杂志

This study aims to investigate the effect of Huaier aqueous extract on the growth and metastasis of human non-small cell lung cancer NCI-H1299 cells and its underlying mechanisms. MTT assay was used to detect the effect of Huaier aqueous extract on the proliferation of NCI-H1299 cells. Flow cytometry was used to examine the effect of Huaier aqueous extract on the apoptosis, cell cycle, and ROS level of NCI-H1299 cells. Wound healing assay was used to evaluate the effect of Huaier aqueous extract on the migration ability of NCI-H1299 cells. Western blot was used to detect the levels of proteins involving apoptosis, epithelial-mesenchymal transition(EMT), and MAPK signaling pathway in NCI-H1299 cells exposed to Huaier aqueous extract. The results showed that Huaier aqueous extract inhibited the proliferation of NCI-H1299 cells, and induced cell-cycle arrest at the phase S. Huaier aqueous extract promoted the apoptosis of NCI-H1299 cells by down-regulating the expression of anti-apoptotic protein Bcl-2. Moreover, Huaier aqueous extract increased ROS level and induced ferroptosis in NCI-H1299 cells. EMT played a critical role in cancer metastasis. Huaier aqueous extract reduced the migration ability of NCI-H1299 cells by inhibiting EMT of NCI-H1299 cells. In addition, this study revealed that Huaier aqueous extract inhibited MAPK signaling pathway in human non-small cell lung cancer NCI-H1299 cells, which may be one of Huaier's mechanisms in inhibiting growth and metastasis of NCI-H1299 cells. This study provides a new theoretical basis for the clinical treatment of lung cancer with Huaier, and important reference significance for further studies on the anti-tumor mechanisms of Huaier.

Protective effect of extractum trametes robiniophila murr on puromycin aminonucleoside-induced podocyte injury in vitro of mice and its mechanism / 吉林大学学报(医学版)

Objective: To investigate the effects of extractum trametes robiniophila murr on the filtration rate, motility and cytoskeleton rearrangement of the podocytes invitro of the puromycin aminonucleoside (PAN) - treated mice, and to clarify the protective effect of extractum trametes robiniophila murr on the podocyte injury and its mechanism. Methods: The podocytes cultured in vitro were randomly divided into control group, model group and test group. The podocytess in model group were treated with 50 mg · L-1 PAN for 24 h; the podocytess in test group were treated with 10 g · L-1 extraction trametes robiniophila murr for 1 h and then treated with 50 mg · L-1 PAN for 24 h. The filtration rate of podocytes to FITC-BSA was measured by two-compartment diffusion system; the scratch repair rate of podocytes was detected by cell scratch test, and the number of podocytes passing through the membrane was measured by Transwell cell migration test. Laser confocal microscope was used to observe the cytoskeleton rearrangement of podocyte cytoskeleton protein F-actin labeled with Invitrogen phalloidin directly. Results: Compared with control group, the FITC-BSA filtration rate of the podocytes in model group was increased significantly (P<0. 01); compared with model group, the FITC-BSA filtration rate of the podocytes in test group was decreased significantly (P<0. 01). Compared with control group, the scratch repair rate of podocytes and the number of transmembrane cells in model group were transmembrane (P<0. 05); compared with model group, the scratch repair rate of podocytes and the number of migration migration cells in test group were decreased significantly (P<0. 05). Compared with control group, the expression level of F-actin in the podocytes in model group was decreased significantly (P<0. 01), the rearrangement rate of F-actin was increased signifiantly (P< 0.01), and the structure of podocyte cytoskeleton was disordered; compared with model group, the expression level of F-actin in the podocytes in test group was increased significantly (P<0. 01), the rearrangement rate of F-actin was decreased significantly (P < 0. 01), and the skeleton rearrangement was alleviated obviously. Conclusion: Extractum trametes robiniophila murr could reduce the filtration rate of podocytes to BSA invitro under the pathological condition, and its possible mechanism is that extractum trametes robiniophila murr reduces the motility of podocytes and improve the rearrangement of podocyte cytoskeleton in vitro.

Killing effect of Huaier combined with DC-CIK on nude mice bearing colon cancer HT29 stem cells / 中国中药杂志

To compare the therapeutic effects of different treatment methods on the nude mice bearing colon cancer HT29 cells. BalB/C nude mice colon cancer stem cell models were established and randomly divided into the following four groups, with 8 nude mice in each group: blank control group, DC-CIK group, Huaier group, and Huaier combined with DC-CIK group (combined treatment group). The mice in DC-CIK group and combined treatment group received 1×10⁶ DC-CIK cells treatment by tail vein injectionafter the tumor stem cells were inoculated for 4 days,2 times a week for three weeks. The mice in Huaier group and combined treatment group received intragastric administration at the dose of 20 g/60 kg body weight, 0.2 mL/time, once a day for a total of three weeks. The mice in control group received equal volume of normal saline. Tumor size and body weight of nude mice were measured every 2 days during treatment for three weeks in each group. After the treatment, the nude mice were sacrificed to measure the tumor weight and the tumor inhibition rate was calculated. The RT-PCR method was used to detect the expression levels of the key genes in the signal pathway. After the end of the treatment, the quality of the tumor in the Huaier group, DC-CIK group and combined treatment group was significantly lower than that in the control group; the quality in combined treatment group was significantly lower than that in Huaier group and DC-CIK group.Among them, the tumor inhibition rate reached 46.77% in the combined treatment group. In respect of changes in expression levels of key genes in the signaling pathway, the mRNA expression levels of key genes PI3KR1 and Akt in PI3K/Akt pathway, key genes Wnt1 and CTTNB1 in Wnt/-catenin pathway, and key genes Notch1, Notch2, Notch3 in Notch pathway in the combined treatment group were lower than those in DC-CIK group and Huaier group. The Huaier combined with DC-CIK group showed best therapeutic effect among different treatment methods for HT29 stemcell colon tumors in nude mice, providing a new idea for clinical treatment of colon cancer.

Huaier aqueous extract inhibits proliferation of human hepatoma SK-HEP-1 cells through up-regulation of autophagy / 中国中药杂志

The purpose of this study was to investigate the effect of Huaier on autophagy of human hepatoma SK-HEP-1 cells and the effect of autophagy on the proliferation of SK-HEP-1 cells. CCK-8 assay was used to evaluate the effect of Huaier on the proliferation of SK-HEP-1 cells under different concentrations and different times. Acridine orange staining was used to measure the effect of Huaier on the autolysosome formation in SK-HEP-1 cells. Immunofluorescence assay was applied to examine the effect of Huaier on the expression and distribution of autophagy marker LC3 in SK-HEP-1 cells. In addition， LC3 expression was also checked by immunoblot analysis in the presence of Huaier. At last， the effects of Huaier in combination with autophagy inhibitor bafilomycin A1 on the proliferation of SK-HEP-1 cells was detected by CCK-8 assay. The results showed that Huaier aqueous extract significantly inhibited the proliferation of human hepatoma SK-HEP-1 cells in a dose- and time-dependent manner. Huaier aqueous extract dramatically promoted the formation of autolysosome in SK-HEP-1 cells. Moreover， Huaier markedly increased the number and intensity of intracellular LC3 fluorescent puncta and up-regulated LC3-Ⅱ expression. These data indicated that Huaier evidently activated autophagy of SK-HEP-1 cells. Additionally， autophagy inhibition significantly attenuated the sensitivity of SK-HEP-1 cells to Huaier treatment. Therefore， autophagy activation is involved in the inhibitory effects of Huaier on the proliferation of human hepatoma SK-HEP-1 cells.

Research advances in Huai'er granules combined with transarterial chemoembolization in treatment of hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) has an insidious onset and when a confirmed diagnosis is made,most patients lose the chance for surgery and are given transarterial chemoembolization (TACE) as palliative treatment.However,repeated TACE may lead to overexpression of hypoxia-inducible factor 1 α (HIF-1 α) and vascular endothelial growth factor (VEGF),liver injury,and reduced immune function and has poor long-term efficacy.The introduction of Huai'er granules may help to change the current status.Studies in China and foreign countries have shown that Huai'er granules exert a remarkable anti-tumor effect by blocking cell cycle,inducing cell apoptosis,inhibiting cell proliferation and invasion,and blocking the hepatitis B-hepatocellular carcinoma pathway.Meanwhile,as an adjuvant drug for HCC,Huai'er granules cover the shortcomings of TACE from multiple aspects and can effectively inhibit the overexpression of HIF-1o and VEGF,improve liver injury and immunity,enhance the effect of chemotherapy drugs,and reverse drug resistance.Many clinical studies have confirmed the remarkable advantages of Huai'er granules combined with TACE,and their synergistic effect helps to enhance anti-tumor effect and improve short-and long-term survival rates.

Trametes Robiniphila Murr. and Hepatocellular Carcinoma / 日本補完代替医療学会誌

Although introduced to Japan as a health food, Huaier granule emerged with abundant evidence, both from fundamental and clinical researches, and is being prescribed clinically in China, since it was originally developed as a new pharmaceutical. Huaier granule has a wide range of application and this review narrow down to the effects of it to hepatocellular carcinoma, the most reported one.

Study on effect and mechanism of Huaier aqueous extract on growth and invasion of human prostate cancer PC3 cells / 中国中药杂志

The purpose of this study was to investigate the effect and mechanism of Huaier aqueous extracton growth and invasion of human prostate cancer PC3 cells. CCK-8 assay was used to evaluate the inhibitory effect of Huaier aqueous extract on proliferation of PC3 cells. The effects of Huaier aqueous extract on cell cycle and apoptosis of PC3 cells were analyzed by flow cytometry. Moreover, wound healing assay and Transwell assay were performed to determine the effect of Huaier aqueous extract on invasion and migration abilities of PC3 cells. PC3 cells treated with Huaier aqueous extract were subjected to western blotting for protein levels of EMT markers and phosphorylation levels of key proteins in MAPK pathway. Results revealed that Huaier aqueous extract significantly inhibited the proliferation of PC3 cells in a dose-dependent and time-dependent manner. Huaier aqueous extract dramatically increased the apoptosis rate and induced S-phase arrest in PC3 cells.Furthermore, Huaier suppressed invasion and migration abilities of PC3 cells, and facilitated MET process of PC3 cells via down-regulation of N-cadherin and TCF8/ZEB1 and up-regulation of E-cadherin. In addition, Huaier reduced the phosphorylation of JNK and ERK. Therefore, the regulatory effects of Huaier on EMT and MAPK pathway may be responsible for the suppressive effect of Huaier on growth and invasion of PC3 cells.

Effect of Huaier Granules on Invasion and Metastasis of Colorectal Cancer SW480 Cells in vitro / 医药导报

Objective To investigate the effects of huaier granules on invasion and metastasis of colorectal cancer SW480 cells in vitro, and explore the basic mechanism. Methods The appropriate concentration and duration of huaier granules promoting SW480 cell apoptosis were determined by SubG1 method. Wound healing assay and transwell assay were used to observe the effect of huaier granules on SW480 cell invasion and metastasis. The changes of E-cadherin, twist, snail and vimentin at protein and mRNA levels were examined by Western blotting and Real-Time PCR. Results After treatment with huaier granules at 3. 0 g·L-1 for 36 h, apoptosis of SW480 cells was most significant, and wound healing assay revealed that relative mobility was (31. 36±2. 39)%, compared with (61. 11±1. 09)% in control group (P<0. 01). Number of invaded cells per field of view was (129±12) in treatment group and (354±20) in control group (P<0. 01). After treatment with huaier granules at 3. 0 g·L-1 for 36 h, protein and mRNA levels of E-cadherin were increased, while those of twist, snail and vimentin were decreased. Conclusion Huaier granules can inhibit invasion and metastasis of colorectal cancer SW480 cells in vitro through effectively depressing epithelial-mesenchymal transition.

Effects of Huaier Granule combined with TAC chemotherapy on immunologic function and prognosis in triple negative breast cancer patients after operation / 国际外科学杂志

Objective To investigate the effects of Huaier Granule combined with TAC chemotherapy on immunologic function and prognosis in triple negative breast cancer patients after operation.Methods Ninty-two cases of Ⅰ-ⅢA stage triple negative breast cancer patients entered the study.They were randomly divided into control group and research group.Only TAC chemotherapy was affected in control group of 42 cases, while Huaier Granule combined with TAC chemotherapy was applied in research group of 50 cases.And we gave Huaier Granule to patients in the first day of chemotherapy.The changes of T cell subset, NK cell were detected in the patients respectively in the first day before therapy and after therapy.The five-year disease-free survival rate and overall survival rate were also observed in two groups.Results Compared with control group, the changes of T cell subset, NK cell had no significant differences in research group in the first day before therapy(P ＞0.05).In the first day after therapy, the level of CD4 + (38.16 ± 5.71) ％ in control group was significantly lower than that (44.67 ± 6.47) ％ in research group(P ＜ 0.05).However, the percentage of CD8 + T cells (28.68 ± 4.06) ％ in control group was markedly higher than that (22.85 ± 3.22) ％ in research group (P ＜ 0.05).The level of NK cell (15.75 ± 3.47) ％ in control group was obviously lower than that (19.46 ± 4.22) ％ in research group(P ＜ 0.05).The five-year disease-free survival rate is 28.6％ in control group, however the five-year disease-free survival rate is 42.0％ in research group, there were significant differences between two groups(P ＜ 0.05).Furthermore, the five-year overall survival rate in research group was obviously higher than that in control group(P ＜ 0.01).Conclusions Huaier Granule combined with TAC chemotherapy not only enhances immune function but also improves prognosis and quality of life in triple negative breast cancer patients after operation.It provides a positive exploration for anti-cancer research by integration of traditional and western medicine.

Application of Huaier Products to Noncancer-Related Fields / 日本補完代替医療学会誌

It has been almost ten years since Huaier products were first introduced to Japan as a health food. Due to its positive results on tumor treatment, Huaier became a notable Traditional Chinese Medicine and even, doctors of Kampo Medicine, Complementary and Alternative Medicine, and Integrative Medicine in Japan are gradually becoming aware of it. In fact, Huaier products have also been confirmed to be effective against noncancer-related diseases, such as respiratory and kidney diseases. In this paper, we summarized and discussed in detail scientific evidences supporting its application to diseases other than cancer.<br>

Influence of sirolimus based triple anti-tumor therapy on T lymphocyte of rat model with liver cancer recurrence after transplantation / 器官移植

Objective To explore the influence of triple anti-tumor therapy which bases on sirolimus combined huaier granule and thymosin α-1 on T lymphocyte of rat model with liver cancer recurrence after transplantation.Methods Seventy-two Sprague-Dawley(SD)rats were randomly divided into triple therapy group,sirolimus group,huaier-granule group,thymosin α-1 group,positive-control group and blank group (n=1 2 in each group).Except the blank group,rats in all the other groups were established the simulation animal model of liver cancer recurrence after liver transplantation by chemical-induced method.After the model was established,rats in the positive control group were executed to appraise whether the model was successful.The proportion of regulatory T cells (Treg)of CD4 + T lymphocytes in peripheral blood (Treg%),the percentage of CD4 + T lymphocyte of total lymphocyte(CD4 +T%)and the percentage of CD8 + T lymphocyte of total lymphocyte (CD8 +T%),were detected by the flow cytometry respectively.The relationship between Treg% and CD4 + T %,CD8 + T %,the ratio of CD4 +/CD8 + T lymphocytes(CD4 +/CD8 +)was analyzed by the method of Spearman rank correlation.Results Pathological section of rat liver tissue suggested that the rat model was established successfully.Treg % of positive control group was higher than that of blank group,the difference had statistical significance(P <0.05).Treg% of triple therapy group was significantly lower than that of the positive control group,huaier-granule group,thymosin α-1 group,and significantly higher than the blank group (all in P <0.05 ).Compared with positive-control group,CD4 +T% and CD8 +T% of triple therapy group,sirolimus group and thymosin α-1 group were significantly higher (all in P <0.05).CD4 +T%and CD8 +T% of triple therapy group were significantly higher than those of thymosin α-1 group,sirolimus group and huaier-granule group(all in P <0.05).The relationship between Treg% and CD4 +T%,CD8 +T%, CD4 +/CD8 + in peripheral blood were negatively correlated for rats in each group.In addition,the triple anti-tumor therapy decreased the negative correlation between Treg% and CD4 +/CD8 +.Conclusions Sirolimus based triple anti-tumor therapy can decrease the peripheral blood Treg level of the liver cancer rat,increase the number of T lymphocyte and CD4 +/CD8 +,and play the role of anti tumor cell growth and proliferation.

Huaier granules combined with intraarterial chemoembolization for the treatment of hepatocellular carcinoma / 中华普通外科杂志

Objective To evaluate the safety and efficacy of combined transcatheter intraarterial chemoembolization with 350-560 μm gelatin sponge particles and lobaplatin (GSPs-TACE) and oral Chinese herb medication Huaier granules in patients with hepatocellular carcinoma (HCC).Methods This is a case-control,single-institution clinical trial.31 HCC patients receiving GSPs-TACE (group A) were matched with 31 patients receiving GSPs-TACE and Huaier granules (group B).Tumor response was evaluated by CECT using response evaluation criteria in solid tumors at 1 month after initial GSPs-TACE.The overall survival was calculated from the data of initial GSPs-TACE using the Kaplan-Meier method.Results The overall mean follow-up period was 28.7 (range 12-42) months.The overall 6-and 12-month survival rates in group A and group B were 90.3％ and 80.6％ vs 100％ and 93.5％,respectively.There was statistically significant difference in 12-month survival rates (x2 =5.213,P ＜0.05).Median survival time respectively was 17.1 and 20.6 months(x2 =0.745,P ＞0.05).The average TACE times were (4.1 ±7.3) and (2.9 ±8.7) respectively in group A and group B (P =0.01).Tumor objective response rate was statistically different in 6-and 12-month in two arms(x2 =5.945,6.384,P ＜0.05).There was no statistically significant difference in complications (respectively x2 =0.435,0.485,2.037,0.137,0.325,all P ＞ 0.05).Conclusions Huaier granules combined with transcatheter intraarterial chemoembolization with 350-560 μm gelatin sponge particles and carboplatin for HCC is safe and effectively prolongs patients' survival.

Adiuvant huaier on long-term survivals after curative hepatectomy for primary liver cancer / 中华肝胆外科杂志

Objective To study the effects of adjuvant Huaier on long-term survivals after curative partial hepatectomy for primary liver cancer.Methods 175 patients with primary liver cancer who received curative partial hepatectomy from January 2002 to January 2006 were divided into two groups:the treatment group (group A,n =87) and the control group (group B,n=88).Group A was treated with Huaier (60 g per day for 6 months) after the operation while group B received no Huaier treatment.Results The overall 1-,3- and 5 year survival rates and disease-free survival rates were 91.90％,73.90％,and 56.0％ and 68.1％,48.4％ and 40.2％,respectively.The overall 1-,3-and 5-year survival rates in group A were significantly higher than group B (91.80％,79.30％,65.2％ vs 92.0％,68.3％,46.6％,P 0.038).In addition,the 1-,3-and 5-year survival rates after tumor recurrence in group A was also significantly higher than group B (78.6％,46.9％,38.2％ vs 69.0％,16.8％,12.6％,P=0.040).Multivariate analysis showed that the use of Huaier,hepatitis infection,severity of cirrhosis,vascular cancer thrombus were the most important prognostic factors for overall long-term survival (P＜0.05).Blood transfusion and histological grade were independent risk factors for disease free survival.The use of Huaier and the clinicopathological type were significantly co-related to the survival from recurrence/metastasis to death.Conclusion The use of Huaier improved disease free survival and the survival from recurrence or metastasis for patients with primary liver cancer following curative hepatectomy.

Observation on the clinical effiect of Aidi injection and Huaier particles combined with interventional therapy for primary liver cancer / 中国基层医药

Objective To observe the clinical effiect and toxicity of Aidi injection and Huaier particles combined with interventional therapy for primary liver cancer patients.Methods 43 paients with primary liver cancer were randomly divided into two groups:the treatment group 22 cases(Aidi injection and Huaier particles combined with interventional therapy to the primary liver cancer)and the control group 21 cases(treated only with intervention therapy of liver cancer).The recent efficiency and toxicity of the two groups were compared.Results The effective rate of the treatment group was 59.1%,and in control group was 33.3%,and the differences was significant(P＜0.01).In the treatment group,clinical benefit rate was 86.4%higher than than of the control group(71.4%),and the difference was significant(P＜0.05);The treatment group significantly improved the quality of life of patients,T cell and NK cell activity were improved,and better than the control group(P＜0.05).The incidence of gastrointestinal reactions and neutropenia rate in treatment group was lower than the control group(all P＜0.05).Conclusion Aidi injection and Huaier Granule interventional therapy could improve the curative effect of primary liver cancer、the immune activity、quality of patients life,and the adverse effects.

Inhibitory Effect of Extract of Fungi of Huaier on Hepatocellular Carcinoma Cells / 华中科技大学学报（医学）（英德文版）

This study investigated the inhibitory effect of the extract of fungi of Huaier (EFH) on the growth of hepatocellular carcinoma (HCC) cells.Hep-G2 cells,a human HCC cell line,were cultured in DMEM containing 10% fetal bovine serum and treated with EFH of different concentrations (1,2,4,8 mg/mL) for 24,48 and 72 h respectively.The apoptosis rate of the cells was flow cytometrically measured.Thirty-six tumor-bearing New Zealand rabbits were randomly divided into 3 groups:group A (control group),in which the rabbits were infused with 0.2 mL/kg normal saline via the hepatic artery;group B (transhepatic artery chemoembolization [TACE] group),in which the rabbits were given lipiodol at 0.2 mL/kg plus MMC at 0.5 mg/kg via the hepatic artery;group C (TACE +EFH group),in which EFH (500 mg/kg) were orally administered after TACE.Two weeks after TACE,the rabbits were sacrificed and the implanted tumors were sampled.The tumor volume and the necrosis rate were determined.The tumor tissues were immunohistochemically detected for the expressions of factor Ⅷ,VEGF,P53,Bax and Bcl-2.The microvessel density (MVD) was calculated by counting the factor Ⅷ-positive endothelial cells.Our results showed that after treatment with EFH,the apoptosis rate of Hep-G2 cells was enhanced in a concentration- and time-dependent manner.Two weeks after the treatment,the average tumor volume,the necrosis rate and the growth rate of the implanted tumor in group C were significantly different from those in groups A and B (P<0.05).MVD and VEGF expressions were significantly decreased in the group C when compared with those in groups B (P<0.05 for all).The Bax expression was weakest in group A and strongest in group C.The expressions of P53 and Bcl-2 were minimal in group C and maximal in group A.There were significant differences in the expressions of P53,Bax and Bcl-2 among the 3 groups (P<0.05 for all) and there was significant difference between group B and group C (P<0.05).It was concluded that EFH could suppress not only the growth of HCC cells but also tumor angiogenesis and it can induce the apoptosis of HCC cells.EFH serves as an alternative for the treatment of HCC.

Effects of huaier granule on hepatocellular carcinoma after Hver transplantation / 中华消化外科杂志

Objective To investigate the auxiliary effects of huaier granule on hepatoeellular carcinoma (HCC)patients after liver transplantation.Methods Sixty HCC patients who had undergone liver transplantation from Julv 2004 to June 2006 and met the standard of UCSF were involved in this study.All patients were divided into huaier granule group(n=20),chemotherapy group(n=15),huaier granule+chemotherapy group (n=15)and control group(n=10).The white blood cell count,liver function,cell immunity and immunologieal reiection were detected.The 1-year tumor recurrence rate wag calculated.Results The white blood cell counts in chemotherapy group 1,3,and 6 months after treatment were significantly lower than that before treatment (F=62.053,58.472,49.807,P＜0.05).The changes of white blood cell counts of the other 3 groups before and aftertreatment were small.The difference on the white blood cell counts of the 4 groups had no statistical 8ignincanee(F=102.361,113.412,87.572,P＜0.05).The NK activity,CD4+/CD8+ ratio,IL-2 level in huaier granule group and huaier granule+chemotherapy group 1,3,6 months after treatment were significantly higher than those before treatment,and were significantly higher than those in chemotherapy group and control group(P＜0.05).No immunological rejection occurred in all the groups.Two patients in each group had recurrence and metastasis of HCC within 1 year after the treatment.and the incidence in control group was higher than the other 3 groups(P＜0.05). Conclusions Humer granule can increase the white blood cell count which is decreased after chemotherapy,impmve cellular immunity,and effectively suppress the recurrence and metastasis of HCC at the first year after operation.

Experimental study of extract of fungi of huaier on angiogenesis in vitro / 中国药理学通报

AIM To investigate the inhibitory effect of extract of fu ng i of huaier (EFH) on neovascularization formed by human umbilical vein endotheli al cells (HUVECs) in vitro. METHODS Using MTT assay, flow cytomet ry and Matrigel assay, the effect of EFH on the proliferation and differentiatio n of HUVECs stimulated by vascular endothelial growth factor (VEGF) were evaluat ed in vitro. RESULTS EFH inhibited proliferation of HUVECs stimul ated by VEGF at the concentration of 0 1 to 10 g?L -1 . The antiproliferat itive effect occurred in a dose-dependent manner. Flow cytometry analyses revea led that EFH treatment delayed S-phase progression. A remarkable inhibition of tube formation was observed in the presence of 1 g?L -1 EFH and complete i nhibition was obtained at 10 g? L -1 EFH. CONCLUSION EFH is able to inhibit neovascularization formed by HUVECs. Its mechanism might be rela ted to S-phase progression.