论文部分内容阅读
目的 :探讨小剂量三氧化二砷(arsenic trioxide,As2O3)联合3’-叠氮-3’-脱氧胸腺嘧啶核苷(3’-azido-3’-deoxythymidine,AZT)对肝癌HepG2细胞增殖和凋亡的作用及其可能的作用机制。方法 :应用MTT法检测不同浓度As2O3、AZT和As2O3联合AZT对人HepG2细胞的增殖抑制作用并计算联合指数,FCM法检测As2O3、AZT和As2O3联合AZT干预后HepG2细胞的凋亡率,RT-PCR法和蛋白质印迹法检测As2O3、AZT和As2O3联合AZT干预后HepG2细胞中caspase-3、Bcl-2和Bax mRNA及蛋白的表达水平。结果 :As2O3联合AZT干预后,HepG2细胞的增殖抑制率高于各单药组(P<0.05),As2O3联合AZT的联合指数<1,表现出明显的协同效应。As2O3联合AZT干预组HepG2细胞的凋亡率明显高于对照组(未进行药物干预)和各单药组(P<0.05)。As2O3联合AZT干预组HepG2细胞中caspase-3和Bax mRNA及蛋白的表达水平明显高于对照组和各单药组(P<0.05),As2O3联合AZT干预组HepG2细胞中Bcl-2 mRNA和蛋白的表达水平明显低于对照组(P<0.05),As2O3联合AZT干预组HepG2细胞中Bax mRNA和蛋白表达水平与Bcl-2 mRNA和蛋白表达水平间的比值高于对照组(P<0.05)。结论 :As2O3联合AZT可协同抑制HepG2细胞的增殖,这一作用可能与诱导细胞凋亡、上调caspase-3和Bax表达以及下调Bcl-2表达有关。
AIM: To investigate the effect of arsenic trioxide (As2O3) combined with 3'-azido-3'-deoxythymidine (AZT) on the proliferation and apoptosis of HepG2 hepatocellular carcinoma cells And its possible mechanism of action. Methods: MTT assay was used to detect the proliferation of HepG2 cells with different concentrations of As2O3, AZT and As2O3 combined with AZT. The apoptotic rate of HepG2 cells was measured by FCM and the apoptosis rates of HepG2 cells treated with As2O3, AZT and As2O3 were detected by RT-PCR The expressions of caspase-3, Bcl-2 and Bax mRNA and protein in HepG2 cells after treatment with As2O3, AZT and As2O3 combined with AZT were detected by Western blotting and Western blot. Results: The proliferation inhibition rate of HepG2 cells was higher than that of the single drug group (P <0.05) after As2O3 combined with AZT. The combined index of As2O3 and AZT <1 showed obvious synergistic effect. The apoptosis rate of HepG2 cells treated with As2O3 combined with AZT was significantly higher than that of the control group (without drug intervention) and with the single drug group (P <0.05). The mRNA and protein expressions of caspase-3 and Bax in HepG2 cells treated with As2O3 combined with AZT were significantly higher than those in control group and each single drug group (P <0.05). The mRNA and protein expressions of Bcl-2 in HepG2 cells treated with As2O3 combined with AZT (P <0.05). The ratio of Bax mRNA and protein expression to Bcl-2 mRNA and protein expression in HepG2 cells treated with As2O3 combined with AZT was higher than that in control group (P <0.05). Conclusion: As2O3 combined with AZT can synergistically inhibit the proliferation of HepG2 cells. This effect may be related to the induction of apoptosis, the up-regulation of caspase-3 and Bax, and the down-regulation of Bcl-2 expression.