维生素E联合顺铂抑制肝癌细胞BEL-7402体外增殖作用及其机制

目的 观察维生素E联合顺铂对肝癌细胞株BEL-7402体外增殖的抑制作用并探讨其作用机制.方法 将不同浓度的顺铂及维生素E作用于BEL-7402细胞,观察细胞增殖抑制率.采用逆转录-聚合酶链反应(RT-PCR)方法分析信号转导与转录激活因子-3(STAT3)mRNA的表达.应用流式细胞术、免疫组织化学等方法检测细胞的凋亡.结果 单纯化疗对BEL-7402细胞增殖的抑制率分别为(14.3±3.2)%(24 h)、(21.9±3.5)%(48 h),联合组对BEL-7402细胞增殖的抑制率分别为(25.6±4.2)%(24 h)、(43.3±5.1)%(48 h),两者之间差异均有统计学意义(P<0.05).对照组、单纯化疗组、联合组肝细胞STAT3 mRNA表达水平分别为0.875±0.106、0.726±0.083、0.135±0.018,对照组与单纯化疗组比较差异无统计学意义(P>0.05),单纯化疗组与联合组之间差异有统计学意义(P<0.01).单纯化疗组细胞凋亡率(7.62±0.89)%、G_1期细胞比例(39.98±3.65)%,联合组细胞凋亡率(15.98±1.03)%、G_1期细胞比例(56.23±3.32)%,两者之间差异均有统计学意义(P<0.05).单纯组Fas、bcl-2蛋白表达阳性率分别为(16.8±1.3)%、(30.2±3.8)%,联合组Fas、bcl-2蛋白表达阳性率分别为(32.5±3.6)%、(15.5±1.2)%,两者之间差异均有统计学意义(P<0.05).结论 维生素E联合顺铂可显著抑制BEL-7402细胞的生长增殖,其机制可能与下调STAT3 mRNA的表达,阻滞肿瘤细胞信号转导通路有关.

Inhibitory effects of the combination of vitaminE and cisplatin on the in vitro proliferation of BEL-7402 cells and the mechanisms

Objective To investigate the suppressive effects of vitamin E combined with cisplatin on the proliferation of hepatocellular carcinoma cell line BEL-7402 in vitro and the mechanisms. Methods The BEL-7402 cells were treated with different concentrations of vitamin E and eisplatin, and the inhibition rate of cell proliferation was tested. Cell apoptosis was observed by flow cytometry and immunohistochemis-try. RT-PCR was applied to detect the expression of STAT3 mRNA. Results The inhibition rate of cell proliferation was (14.3±3.2)% (24 h),and (21.9±3.5)% (48 h) in simple chemotherapy group,while that was (25.6±4.2)% (24 h), and (43.3±5.1)% (48 h) in combined chemotherapy group (P<0.05). The expression of STAT3 mRNA (0.135±0.018) was significantly lower in combined chemotherapy group than that (0. 726±0.083) in simple chemotherapy group (P<0.01). However,there was no difference between simple chemotherapy group and control group (P > 0.05). The apoptosis rate in simple chemotherapy group (7.62±0.89)% was obviously lower than in combined chemotherapy group (15.98±1.03)%, P<0.05]. The ratio of cells in G_1 phase (39.98±3.65)% in simple chemo-therapy group was obviously lower than in combined chemotherapy group (56.23±3.32)%, P<0.05].Meanwhile,the expression rate of Fas gene,and bcl-2 protein was (0. 168±0. 013)%,and (0.302±0.038)% in simple chemotherapy group,and that was (0.325±0.036)%,and (0.155±0.012)% in combined chemotherapy group (P<0.05). Conclusion Undonhtedly,vitamin E combined with cisplatin greatly inhibits BEL-7402 cell proliferation probably by down-regulating the expression of STAT3 mRNA,and blocking signal transduction pathway of cancer cells.