BET蛋白抑制剂JQ1增强索拉非尼对肝癌细胞的增殖抑制研究

BET protein inhibitor JQ1 enhances the proliferation inhibition of sorafenib on liver cancer cells

目的探讨BET家族小分子抑制剂JQ1联合索拉非尼对肝癌细胞增殖、凋亡的影响及其作用机制。方法采用MTT法检测索拉非尼、JQ1以及JQ1联合索拉非尼作用于人肝癌细胞HepG2和Bel-7402的增殖抑制率,采用流式细胞术检测细胞凋亡率的变化,Western blot方法检测c-MYC、Bcl-2、BIM蛋白表达水平的变化。结果与索拉非尼、JQ1单独用药比较,JQ1联合索拉非尼作用于肝癌细胞的增殖抑制率增加,凋亡率也增加,JQ1联合索拉非尼作用于肝癌细胞后可以下调c-MYC、Bcl-2蛋白表达水平并且上调BIM蛋白表达水平。结论一定浓度JQ1能增强索拉非尼对肝癌细胞的增殖抑制及凋亡作用,其作用机制可能与降低c-MYC、Bcl-2表达,上调BIM表达相关。

Objective To investigate the effect of BET family small molecule inhibitor JQ1 combined with sorafenib on the proliferation and apoptosis of liver cancer cells and its mechanism.Methods The proliferation inhibition rate of sorafenib,JQ1 and JQ1 combined with sorafenib on HepG2 and Bel-7402 human liver cancer cells was detected by MTT assay,the change of apoptosis rate was detected by flow cytometry,the expression of c-MYC,Bcl-2 and BIM proteins was detected by Western blot.Results Compared with sorafenib and JQ1 alone,the proliferation inhibition rate and apoptosis rate of liver cancer cells increased when treated with JQ1 combined with sorafenib,the expression of c-MYC and Bcl-2 protein was down-regulated and the expression of BIM protein was up-regulated after treated with JQ1 combined with sorafenib on liver cancer cells.Conclusion A certain concentration of JQ1 can enhance the proliferation inhibition and apoptosis effects of sorafenib on liver cancer cells,and its mechanism may be related to the down-regulated expression of c-MYC and Bcl-2,and the up-regulated expression of BIM.