摘要
目的探讨索拉非尼联合顺铂(DDP)对肝癌细胞HepG2的抑制作用及其可能分子机制。方法单独及联合给药后以MTT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 blotting观察ERK及pERK蛋白的表达。结果索拉非尼及DDP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DDP分别主要使细胞阻滞于G1及G2期。两药联用后同时阻滞于G1及G2期。联合组凋亡率明显比单药组高(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DDP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 with cisplatin （DDP） on the proliferation of hepatocellular carcinoma cells and explore the molecular mechanisms. Methods The inhibitory effect of sorafenib and DDP treatment on HepG2 cell proliferation in vitro was assessed by MTT assay. The cell cycle changes and the apoptotic rate of the treated cells were detected by flow cytometry, and the expressions of ERK and pERK examined using Western blotting. Results Sorafenib and DDP alone both significantly inhibited the proliferation of HepG2 cells, showing a synergistic effect of their actions in combined use （P〈0.05）. Sorafenib and DDP alone caused cell cycle arrest at G1 and G2 phases, respectively. Combined use of the two drugs resulted in significant reduction of the S-phase cell percentage and cell cycle arrest at G1 and G2 phases. The coadministration of the drugs significantly increased the apoptosis rate of the cells as compared with the that of the cells with sorafenib or DDP treatment alone （P〈0.05）. Sorafenib and DDP, used alone or in combination, did not produce obvious effect on ERK expression. Sorafenib treatment for 24 h reduced pERK expression in the HepG2 cells, and the effect was enhanced by combined treatment with sorafenib and DDP. Conclusions Sorafenib and DDP show a synergistic effect in inhibiting the proliferation and inducing apoptosis of HepG2 cells. The mechanisms of this synergistic effect can be closely related to the double blockage of the cell cycle and Raf/MEK/ERK pathway inhibition.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2008年第9期1684-1687,共4页
Journal of Southern Medical University
关键词
索拉非尼
顺铂
肝癌
联合用药
Sorafenib
cisplatin
hepatocellular carcinoma
coadministration, drug
