目的：研究索拉非尼联合塞来昔布在体外对肝癌HepG2细胞增殖的影响。方法以不同浓度索拉非尼和塞来昔布分别组成单药组和联合用药组作用于HepG2细胞,MTT法检测增殖抑制率,流式细胞仪检测细胞周期。 Western blot检测Cyclin D1、Cyclin D3、CDK4蛋白的表达。结果索拉非尼、塞来昔布单药与联用均能抑制HepG2细胞增殖,呈时间-剂量依赖效应,两药联用有协同效应( P <0．05)。药物组与空白组相比, G0/G1期细胞比例增高,联合用药组最高。联合用药组与单药及空白对照组相比,HepG2细胞中Cyclin D1、Cyc-lin D3蛋白的表达显著降低。结论索拉非尼联合塞来昔布可能通过下调Cyclin D1、Cyclin D3表达,增强G0/G1期阻滞,发挥协同抑制HepG2细胞增殖的作用。%Objective To investigate the effect of sorafenib and celecoxib combination therapy on proliferation of human hepatocellular carcinoma cell line HepG2. Methods HepG2 cells were treated with different concertrations of sorafenib or celecoxib alone or their combination. The inhibitory effects were detected by MTT assay. Cell cycles were analyzed by flow cytometry in different groups. The expressions of cell cycle related proteins Cyclin D1,Cyclin D3,CDK4 were evaluated by Western blot. Results Sorafenib or celecoxib used alone or combination inhibited the proliferation of HepG2 cells in a time-and dose-dependent manner,and a synergistic effects was observed in their com-bined action (P<0. 05). G0/G1 phase cell proportion in medication groups was higher than that in blank group,and G0/G1 phase cell proportion in combination group was the highest. Compared with single drug or blank control group, the combination use could significantly inhibit Cyclin D1 and Cyclin D3 expression in HepG2 cell. Conclusion The combination of sorafenib with celecoxib can inhibit Cyclin D1 and Cyclin D3 expression,increase the G0/G1 phase re-tardation,and play a synergistic inhibitory effect for HepG2 cells.
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