中文摘要：

目的探讨PI3K/Akt和mTOR双重抑制剂BEZ235对HepG2肝癌细胞增殖和凋亡的影响,并观察BEZ235与阿霉素合用的联合作用。方法采用MTT法检测HepG2细胞增殖;流式细胞术分析细胞周期变化;AnnexinⅤ-FITC试剂盒检测细胞凋亡;免疫印迹法检测蛋白表达水平。结果BEZ235 2.5μmol.L-1～7.5μmol.L-1能够抑制HepG2细胞的增殖,且抑制作用呈时间和剂量依赖性。HepG2细胞经BEZ235处理后,细胞阻滞于G1期,cyclinD1表达水平下调,而cyclinB1的表达则不受影响。BEZ235明显增强了阿霉素对HepG2细胞的抑制作用,并促进阿霉素下调β-catenin的表达。结论 BEZ235对人肝癌细胞HepG2的生长具有显著的抑制作用;联合应用BEZ235和DOX协同抑制HepG2细胞的增殖,其机制可能与共同调节β-catenin通路相关。

英文摘要：

Aim To detect the effect of BEZ235,inhibitor of phosphoinositol-3-kinase/Akt and mammalian target of rapamycin,on the cell proliferation and apoptosis in human hepatoma cancer cell line HepG2 cells,and also to investigate the synergistic effect of BEZ235 combined with adriamycin on HepG2 cells.Methods Cell growth was detected by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide（MTT） assay.Cell cycle was analyzed by flow cytometry.Annexin Ⅴ-FITC apoptosis detection kit was used to detect cell apoptosis.Protein expression was examined by Western blot analysis.Results Cell proliferation was inhibited in dose-and time-dependent manner when HepG2 cells were treated with 2.5 μmol·L-1~7.5 μmol·L-1 BEZ235.Flow cytometry results indicated that BEZ235 arrested cell cycle progression at the G1 phase via downregulating the expression of cyclinD1.BEZ235 cotreatment with adriamycin substantially increased cytotoxic effects of adriamycin in hepatoma cells.Conclusions The PI3K/mTOR dual inhibitor BEZ235 shows substantial anti-tumor activity in human hepatocelluar carcinoma cell line HepG2,and down-regulates the expression of β-catenin which probably is the potential mechanism for the synergistic effect of BEZ235 and adriamycin in hepatocellular carcinoma.