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Herbal formula of Bushen Jianpi(补肾健脾方)combined with sorafenib inhibits hepatocellular carcinoma growth by promoting cell apoptosis and blocking the cell cycle

查看全文 作　　者：ZHOU [1]Zhangjie;LIU [3]Xinhua;WU [1]Tingting;QUE [4]Zujue;WU [3]Zhonghua;WU [5]Weizhong;FU [1]Shujuan;ZHANG [1]Shiqiang;YANG [1]Yun;JIANG [1]Haiyan;XIA [1]Xiaoting;LV [1]Junqiang;DU [1]Boqian;LI [1]Yun;LU [3]Tao;ZHANG [2]Zhihui;ZHONG [1]Yi 高影响力作者 机构地区：[1]Oncology Department,Shanghai TCM-Integrated Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200082,China;[2]Institute of vascular disease,Shanghai TCM-Integrated Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200082,China;[3]Science and Technology Experimental Center,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;[4]Tumor Institute of Traditional Chinese Medicine,Longhua Hospital,Shanghai 200032,China;[5]Institute of Liver Cancer,Zhongshan Hospital Affiliated to Fudan University,Shanghai 200032,China高影响力机构 出　　处：《Journal of Traditional Chinese Medicine》索引2021年第41卷第2期,共9页高影响力期刊 基　　金：Shanghai Science and Technology Commission:a Randomized,Controlled,Double-blind Clinical Study of Xianglian Pill on Immunotherapy of Advanced Malignant Tumor(No.19401971600);Hongkou District Health Committee National Medicine:Traditional Chinese Medicine Oncology Specialty and Comprehensive Treatment Area Project(No.HGY-ZHZL-2018-03);Budget Project of Shanghai University of Traditional Chinese Medicine:Exploring the Mechanism of Berberine Reversing T Cell Failure and Enhancing the Curative Effect of Immunotherapy for Lung Cancer Based on Tox Gene(2020TS101)。 摘　　要：OBJECTIVE:To investigate the efficacy of an herbal formula of Bushen Jianpi(补肾健脾方,BSJP)combined with sorafenib on hepatocellular carcinoma(HCC)in vitro and in vivo,and to study the underlying mechanisms of action.METHODS:BSJP,a mixture of 12 raw herbs,was extracted in 70%alcohol/30%water and freeze-dried into a powder.The in vitro effects of BSJP alone,sorafenib alone,and their combination on cell survival,apoptosis,and cell cycle distribution were evaluated in HCC cell lines HCCLM3,HepG2,and SMMC-7721.The expression of B-cell lymphoma-2(Bcl-2),caspase-3,and caspase-9 in HCCLM3 cells was measured using Western blots after drug administration.The in vivo effects of BSJP and sorafenib were evaluated in a tumor surgical resection model using 4-week old male athymic BALB/c nude mice injected with HCCLM3 cells.Immunohistochemical analysis of tumor tissues was performed to evaluate the effects of BSJP alone,sorafenib alone,and their combination on the expression of caspase-3,caspase-9,and Bcl-2.RESULTS:BSJP decreased the survival rate of HCC cell lines,and the combination of BSJP and sorafenib further decreased the survival rate.BSJP significantly promoted cell apoptosis and blocked cell-cycle progression in HCCLM3,HepG2,and SMMC-7721 cells in a dose-dependent manner.Furthermore,the administration of BSJP and sorafenib inhibited the growth of HCCLM3 cell xenografts in nude mice,with no reduction in body weight.In vivo and in vitro experiments showed that BSJP combined with sorafenib could significantly decrease the expression of Bcl-2.CONCLUSION:Our findings suggest that the herbal formula of BSJP is a potential HCC antitumor agent. 关 键 词：carcinoma,hepatocellular cell apoptosis cell cycle SORAFENIB Bushen Jianpi
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