摘要:目的:探索槐耳清膏对体结肠癌SW480细胞增殖能力影响及其机制。方法:采用噻唑蓝(MTT)比色法检测槐耳清膏对SW480细胞增殖能力的作用,并探求最佳作用浓度;将体外培养细胞随机分为常氧组(NC组)、低氧组(HC组)和低氧槐耳组(HH组),逆转录聚合酶链反应（RTPCR）检测各组血管内皮生长因子(VEGF) mRNA表达水平,Western blot检测蛋白表达水平。结果:槐耳清膏对SW480细胞抑制率随药物浓度增加而上升,1 mg/mL时抑制率最大(66.7%),与氟尿嘧啶组(浓度为10 μg/mL)相比无统计学意义。HH组和HC组VEGF mRNA表达均显著高于NC组,分别为4.71±0.07,4.54±0.02和1.19±0.03(P＜0.05),但HH组与HC组比较差异无统计学意义。HC组VEGF蛋白表达显著高于NC组,分别为0.66±0.03和0.38±0.02(P＜0.05),HH组较HC组VEGF蛋白表达均显著下降,分别为0.37±0.03和0.66±0.03(P＜0.05)。结论:槐耳清膏可抑制SW480细胞增殖,1 mg/mL时抑制率最大。其机制为槐耳清膏下调细胞内VEGF蛋白表达,从而抑制肿瘤生长。Abstract: Objective: To investigate the effect of Huaier cream on proliferation of colon cancer cells SW480 and its mechanism. Methods: The proliferation was analyzed by MTT. SW480 cells were randomly divided into normoxic group (NC group), hypoxia group (HC group) and hypoxia group treated by Huaier (HH group). Levels of mRNA and protein expression of VEGF were detected by RTPCR and Western blot, respectively． Results: Huaier cream induced a dosedependent inhibition of SW480 cells. The maximum percentage of growth inhibition was 66.7% at a concentration of 1.0 mg/mL, but no significant difference was found compared to the positive control (5FU 10 μg/mL). VEGF mRNA levels were significantly higher in HC group and HH group than in NC group (4.71±0.07, 4.54±0.02 vs 1.19±0.03, all Plt;0.05), but not significantly different between HC group and HH group. VEGF protein expression was higher in HC group than NC group (0.66±0.03 vs 0.38±0.02, Plt;0.05). In HH group, VEGF protein was inhibited remarkably compared with HC group (0.37±0.03 vs 0.66±0.03, Plt;0.05). Conclusion: Huaier cream can significantly inhibit SW480 cells and the top inhibition concentration is 1.0 mg/mL. Huaier cream plays a role in inhibiting tumor through downregulating protein expression of VEGF.
Objective To observe the life quality and the immune function of colorectal cancer patients treated by huaier granule combined with FOLFOX4 chemotherapy. Methods A total of 76 cases of colorectal cancer with chemotherapy indications were divided into two groups at random. Huaier granule and FOLFOX4 chemotherapy was applied in trial group， meanwhile， placebo and FOLFOX4 chemotherapy in control group. The changes of life quality， common condition， and immune state in two groups before and after treatment were abserved. Results The effective rate in the trial group was 92.1％ （35/38）， and in the control group was 65.8％ （25/38）， χ2=7.91， P＜0.005. The life quality improving rate in the trial group was 78.9％ （30/38）， and in the control group was 31.6％ （12/38）， χ2=6.33， P＜0.05. The CD3 increase rate in the trial group was 65.8％（25/38）， and in the control group was 23.7 ％ （9/38）， χ2=7.96， P＜0.005， the CD4/CD8 increase rate in the trial group was 68.4 ％（26/38） , and in the control group was 28.9％ （11/38）， χ2=10.53， P＜0.005. Conclusions Huaier granule can significantly improv the clinical symptoms, life quality, and immune state. Huaier granule combined with FOLFOX4 chemotherapy is a new effective scheme to cure colorectal cancer， is worth further generalization．
Objective To study the effect of Huaier granule on the recurrence and metastasis of hepatocellular carcinoma (HCC) and immune rejection in the postoperative patients with liver transplantation for HCC. Methods Twenty-eight patients of liver transplantation for HCC who had taken Huaier granule orally for more than 6 months from September 2001 to March 2007 in West China Hospital were included as treatment group, and other 56 patients of liver transplantation for HCC who didn’t take any Huaier granule in the same time were included as the control group according to the same stage of TNM, degree of tumor differentiation (Edmondson grading) respectively with the treatment group. The method of retrospective cohort study was used to compare the incidence of immune rejection and the 6-month, 1-year, and 2-year recurrence and metastasis of HCC, disease free survival rate, and survival rate between two groups after 2 years’ follow-up beginning from the date of surgery. Results The 6-month, 1-year, and 2-year tumor recurrence and metastasis incidences in treatment group were 14.3%, 32.1%, and 39.3% respectively, which were 23.2%, 32.1%, and 50.0% respectively in control group, and the 2-year tumor recurrence and metastasis incidence of the treatment group was lower than that of the control group. The 6-month, 1-year, and 2-year disease free survival rates in treatment group were 85.7%, 67.5%, and 60.0% respectively, which were 76.7%, 67.6%, and 49.3% respectively in control group, and the 2-year disease free survival rate of treatment group was higher than that of the control group. The 6-month, 1-year, 2-year survival rates in treatment group were 92.9%, 78.6%, and 67.9% respectively, which were 89.3%, 75.0%, and 62.5% respectively in control group. But the 2-year tumor recurrence and metastasis incidence (P=0.353), 2-year disease free survival curve (P=0.386), and 2-year survival curve (P=0.620) were not significantly different between two groups. The incidence of immune rejection was 14.29% in the treatment group and 16.07% in the control group, which was not significantly different between the two groups (P=0.831). Conclusions Huaier granule can increase the 2-year tumor-free survival rate and restrain the recurrence and metastasis of HCC, and does not increase the incidence of immune rejection. Huaier granule as a treatment of HCC in patients with liver transplantation is safe and effective.
ObjectiveTo compare the efficacy and safety of Huaier and Sorafenib in treatment of small hepatocellular carcinoma(HCC)following radical resection. MethodsEighty-two patients with small HCC accepted radical liver resection and then taken Huaier or Sorafenib were collected retrospectively. These patients were divided into Huaier group(51 cases)and Sorafenib group(31 cases)according to the different administration drugs after operation. The baseline characteristics, tumor characteristics, survival rate, tumor recurrence rate, and side effects were compared between two groups. Results①There were no significant differences on the baseline demographic characteristics, liver function, and tumor characteristics between two groups(P > 0.05).②The overall survival rate and tumor-free survival rate had no significant differences between the Huaier group and the Sorafenib group(P=0.737, P=0.699).③The rate of recurrence or metastasis had no significant difference between the Huaier group and Sorafenib group(37.3% versus 32.3%, P=0.648). The most common site of the recurrence or metastasis was the liver and the lung followed.④There were only 5 cases suffered side effects after taking Huaier and no case needed Huaier discontinuance. However, 11 cases suffered side effects after taking Sorafenib and 3 cases needed Sorafenib discontinuance, and the rate of the side effect in the Sorafenib group was much higher than that in the Huaier group(35.5% versus 9.8%, P=0.026). ConclusionFor the small HCC who accepted radical liver resection, Huaier seems to be an effective and safe drug.
ObjectiveTo investigate the effects of Huaier granule combined with systemic chemotherapy on immunologic function and prognosis for advanced breast cancer patients. MethodsNinety-eight cases ofⅣstage breast cancer from March 2006 to March 2009 in this hospital were divided into control group and research group. Only systemic chemotherapy was performed in the control group, while Huaier granule combined with systemic chemotherapy was applied in the research group, and Huaier granule was given on day 1 systemic chemotherapy start. The changes of T lymphocyte subsets and IL-2 level were detected on day 1 before systemic chemotherapy and on month 6 after Huaier granule combined with systemic chemotherapy. The fatality rate and median survival time were also observed between two groups. ResultsCompared with the control group, the changes of T lymphocyte subsets and IL-2 level had no signi-ficant differences on day 1 before systemic chemotherapy between these two groups(P > 0.05). On month 6 after Huaier granule combined with systemic chemotherapy, the CD4+, CD4+/CD8+ T lymphocyte, and IL-2 level were significantly increased, the CD8+ T lymphocyte was significantly decreased in the research group as compared with the control group〔CD4+:(47.35±6.23)% versus(41.33±5.61)%, P < 0.05; CD4+/CD8+: 1.84±0.42 versus 1.47±0.33, P < 0.05; IL-2 level:(1.78±0.45)μg/L versus(1.58±0.30)μg/L, P < 0.05; CD8+:(23.26±3.25)% versus(29.77±4.12)%, P < 0.05〕. The rate of chemotherapy complications and fatality rate within 3 years were significantly decreased in the research group as compared with the control group〔rate of chemotherapy complications: 58.3%(28/48) versus 86.0%(43/50), P < 0.01; fatality rate within 3 years: 62.5%(30/48)versus 82.0%(41/50), P < 0.05〕. The median survival time in the research group was significantly longer than that in the control group(33.5 months versus 24.5 months, P < 0.01). ConclusionsThe preliminary results from this study show that Huaier granule combined with systemic chemotherapy could greatly enhance immune function, reduce side-toxicity of chemotherapy and improve prognosis in advanced breast cancer patients. It provides a beneficial exploration for cancer treatment by integration of traditional and western medicine.
ObjectiveTo evaluate therapeutical effects of Huaier granule combined with transcatheter arterial chemoembolization (TACE) following radical resection of primary hepatocellular carcinoma with microvascular invasion. MethodsThe clinical data of 45 cases of primary hepatocellular carcinoma with microvascular invasion underwent Huaier granule combined with transcatheter arterial chemoembolization (TACE) following radical resection from June 2010 to June 2013 in Liaoning Cancer Hospital were retrospectively analyzed. These patients were divided into Huaier granule plus TACE treatment group (20 cases) and simple TACE treatment group (25 cases) according to the postoperative treatment of the patients. The immune function (CD4+/CD8+ ratio and IL-2 level), 1and 3-year tumor recurrence rates and 3-year cumulative survival rate were compared between two groups after operation. Result① The CD4+/CD8+ ratio and IL-2 level had no significant differences between the 2 groups before operation (P > 0.05), which in the Huaier granule plus TACE treatment group were significantly higher than those in the simple TACE treatment group (P < 0.05) on month 3, 6, and 12 after operation.② 1and 3-year tumor recurrence rates in the Huaier granule plus TACE treatment group were significantly lower than those in the simple TACE treatment group[15% (3/20) versus 48% (12/25), P < 0.05; 45% (9/20) versus 80% (20/25), P < 0.05]. ③ The 3-year cumulative survival rate was 75% and 68% in the Huaier granule plus TACE treatment group and the simple TACE treatment group, respectively. The survival curve analysis showed that the 3-year survival rate had a decreased trend, which in the Huaier granule plus TACE treatment group was slightly higher than that in the simple TACE treatment group, but the difference had no statistical significance between the 2 groups (P > 0.05). ConclusionsAlthough the results of this study fails to confirm that Huaier granule plus TACE treatment for primary hepatocellular carcinoma with microvascular invasion following radical resection could significantly improve the 3-year cumulative survival rate, it could effectively decrease the recurrence rate. It is needed larger sample size to further explore in future research.
ObjectiveTo systematically evaluate efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with Huaier granules in treatment of primary liver cancer (PLC).MethodsThe databases including the PubMed, Embase, Cochrane Library, Wanfang Data, CNKI, VIP were searched to obtain the relevant literatures of Huaier granule combined with TACE therapy (Huaier+TACE group) and alone TACE therapy (TACE group) in the treatment of PLC. The short-term curative effects (objective response rate and disease control rate), 6 and 12-month survival rates, immune function change, and adverse reactions were extracted. The RevMan 5.3 software was applied to carry out the meta analysis.ResultsFifteen studies involving 1 781 cases were enrolled in this study, of which 876 cases underwent the Huaier+TACE, 905 underwent the TACE. The meta analysis results showed that the objective response rate and disease control rate, 6 and 12-month survival rates of the Huaier+TACE group were significantly more superior as compared with of the TACE group (P<0.05), the adverse reaction incidence had no significant difference (P>0.05). Compared with the TACE group, the CD4 +/CD8 + of the Huaier+TACE group was significantly improved (P<0.05).ConclusionFrom results of meta analysis, Huaier granule combined with TACE could improve therapeutic effect, increase survival rate, and improve life quality of PLC.
ObjectiveTo investigate the effect of Huaier extract on the proliferation, invasion, and ferroptosis pathways of colorectal cancer (CRC) cells. MethodsThe CRC cell line SW620 was cultured in vitro, and the cells were treated with Huaier extract solution at different concentrations (0, 5, 10, 20, and 50 mg/mL). The cell counting kit 8 was used to detect the proliferation of CRC cells at different concentrations to scree the test dose of the Huaier extract. The Transwell and the scratch assays were used to detect the cell invasion and migration. The reactive oxygen species (ROS), glutathione (GSH), and malondialdehyde (MDA) kits were used to detect the cellular oxidative stress level. The Western blot was used to detect the ferroptosis-related proteins levels, including glutathione peroxidase 4 (GPX4), nuclear factor E2-related factor 2 (NRF2), and high mobility group box-1 (HMGB1). ResultsIn this study, it could statistically inhibit the proliferation of CRC cells after 48 h interfering with Huaier extract at 10, 20 mg/mL concentrations, so we chose 10, 20 mg/mL concentrations as the test dose, 0 mg/L as the control dose. Huaier extract effectively inhibited the migration and invasion abilities of SW620 cells in a dose-dependent manner (Transwell: F=480.0, P<0.001; scratch assay: F=24.3, P=0.001). The level of ROS in the SW620 cells increased with the increase of concentration in a dose-dependent manner (F=806.3, P<0.001). the level of GSH in the SW620 cells decreased with the increase of concentration in a dose-dependent manner (F=35.0, P=0.005), but the level of MDA was highest at 10 mg/mL (F=22.9, P=0.002) . Further the Huaier extract could effectively reduce the expressions of GPX4 (F=74.2, P<0.001), NRF2 (F=32.8, P=0.001), and HMGB1 (F=55.1, P<0.001) in a dose-dependent manner. ConclusionFrom the results of this study, Huaier extract at 10 and 20 mg/mL concentrations can inhibit the proliferation and invasion of CRC SW620 cells by inducing ferroptosis.