氧化槐果碱对肝癌SMMC-7721细胞增殖与凋亡的影响

Effects of oxysophocarpine on proliferation and apoptosis of hepatocellular carcinoma SMMC-7721 cells

目的探讨氧化槐果碱对人肝癌SMMC-7721细胞增殖和凋亡的影响,并探讨其可能介导的信号通路。方法将人肝癌SMMC-7721细胞分为对照组、氧化槐果碱处理组(2、4、8、16、32mmol/L)。将梯次浓度氧化槐果碱作用于肝癌细胞后培养48h;采用倒置显微镜观察细胞形态变化;采用CCK8法检测不同浓度氧化槐果碱对细胞增殖的影响,采用流式细胞术检测氧化槐果碱对细胞凋亡的影响,通过免疫印迹法检测氧化槐果碱对肝癌细胞B细胞淋巴瘤/白血病-2(Bcl-2),Bcl-2相关X蛋白(Bax)及转录激活因子(STAT)3、STAT5表达水平的影响,分析氧化槐果碱对肝癌SMMC-7721细胞可能的作用。结果氧化槐果碱呈剂量依赖性抑制肝癌SMMC-7721细胞的增殖,并且诱导细胞凋亡。并呈剂量依赖性上调促凋亡Bax的表达,下调抗凋亡蛋白Bcl-2、STAT3、STAT5的表达。结论氧化槐果碱对人肝癌SMMC-7721细胞有抑制增殖、诱导凋亡的作用,可能是通过酪氨酸激酶(JAK)/STAT信号通路下调STAT3、STAT5蛋白激酶表达,从而上调促凋亡Bax基因表达,下调抗凋亡Bcl-2基因表达。

Objective To investigate the effects of oxysophocarpine on the proliferation and apoptosis of human hepatocellular carcinoma SMMC-7721 cells and its possible signaling pathways. Methods Human hepatocellular carcinoma SMMC-7721 cells were divided into control group and oxysophocarpine treatment group (2,4,8,16,32 mmol/ L). The effects of different concentrations of oxysophocarpine on cell proliferation were detected by CCK8 method, the effects of oxysophocarpine on cell apoptosis were detected by flow cytometry, and the apoptotic proteins Bax, Bcl-2 were detected by immunoblotting. The effects of signal transduction and transcription activator ( STAT) 3 and STAT5 on the expression level were studied. The possible signaling pathway of sophocarpine oxide on SMMC-7721 cells was analyzed. Results Oxysophocarpine inhibits the proliferation of SMMC-7721 cells in a dose-dependent manner and induces apoptosis. The expression of apoptotic Bax was up-regulated in a dose-dependent manner, and the expression of antiapoptotic proteins Bcl-2, STAT3 and STAT5 was down-regulated. Conclusion Oxysophocarpine can inhibit proliferation and induce apoptosis of human hepatocellular carcinoma SMMC-7721 cells. This may be related to the down-regulation of STAT3 and STAT5 protein kinase expression by tyrosine kinase ( JAK)/ STAT signaling pathway, thus up-regulation of Bax gene expression and down-regulation of Bcl-2 gene expression.