索拉非尼联合奥沙利铂对肝癌HepG2细胞的抑制作用  

The inhibitory effect of sorafenib together with oxaliplatin on the growth of human hepatic carcinoma cell line HepG2 in vitro

作　　者：储玉山[1] 朱小庆[1] 张玉宇[1] 陆小华[1] 曹建民[1] 

机构地区：[1]江苏省南通大学附属医院介入放射科,226001

出　　处：《介入放射学杂志》2011年第10期810-814,共5页Journal of Interventional Radiology

摘　　要：目的探讨索拉非尼联合奥沙利铂(L-OHP)对肝癌细胞HepG2的抑制作用及其可能的分子机制。方法索拉非尼和L-OHP单独及联合给药后以CCK8法测定HepG2细胞的增殖,用流式细胞仪检测细胞周期及凋亡,用Western blot观察ERK及pERK蛋白的表达。结果索拉非尼及L-OHP单药对HepG2均有抑制作用,两药联合具有协同或相加作用(P<0.05)。索拉非尼及L-OHP分别主要使细胞阻滞于G1及S期。两药联用后同时阻滞于G1及S期。联合组细胞凋亡率明显比各单药组高(P<0.05)。单用及联合用药对HepG2细胞ERK表达无明显影响,索拉非尼及联合用药减少pERK的表达。结论索拉非尼和L-OHP对肝癌HepG2细胞有增殖抑制及促凋亡作用,两药联合表现为协同或相加作用,其机制可能与细胞周期的双重阻滞及细胞增殖通路Raf/MEK/ERK的抑制有关。Objective To investigate the inhibitory effect of sorafenib in combination use with oxaliplatin（L-OHP） on the proliferation of hepatocellular carcinoma cells and to explore the possible molecular mechanism.Methods The inhibitory effect of sorafenib together with L-OHP on the growth of human hepatic carcinoma cell line HepG2 in vitro was evaluated by CCK8 assay.The cell cycle changes and the apoptotic rate of the treated cells were determined by flow cytometry,and the expressions of ERK and pERK were observed by using Western blott.Results Both sorafenib and L-OHP when used alone could significantly inhibit the proliferation of HepG2 cells,and a synergistic or adding effect could be achieved when both sorafenib and L-OHP were used together（P 0.05）.Sorafenib and L-OHP could cause cell cycle to stagnate at G1 phase and S phase,respectively.Combined use of the two drugs resulted in cell cycle arresting at G1 phase and S phase.The combination use of the drugs significantly increased the apoptosis rate of the cells as compared with that when only sorafenib or L-OHP was used（P 0.05）.Sorafenib and L-OHP,whether used alone or in combination,did not produce obvious effect on ERK expression.However,pERK expression in the HepG2 cells was significantly lowered after the treatment with sorafenib alone or in combination with L-OHP,especially in the combination use group.Conclusion The combination use of sorafenib and L-OHP shows a synergistic or adding effect in inhibiting the proliferation and inducing apoptosis of HepG2 cells.The mechanism of this synergistic effect may be closely related to the double blockage of the cell cycle as well as to the inhibition of Raf/MEK/ERK pathway.

关 键 词：肝癌 索拉非尼 奥沙利铂 联合用药 协同作用 

分 类 号：R735.7[医药卫生—肿瘤]