索拉非尼联合顺铂对胃癌SGC7901细胞的抑制作用

The Inhibitory Effect of Sorafenib Combined with Cisplatin on Gastric Cancer SGC7901 Cells

目的:探讨索拉非尼联合顺铂(DDP)对胃癌SGC7901细胞的抑制作用以及可能的分子机制。方法:选取人胃癌细胞株SGC7901,用索拉非尼和DDP单药或联合作用于细胞,观察最佳抑制效果。MTT法检测索拉非尼、DDP及两药联用对胃癌SGC7901细胞的增殖抑制作用并计算半数抑制浓度(IC50);用流式细胞仪检测细胞凋亡;用Western blot观察ERK及pERK蛋白的表达。结果:MTT检测结果显示胃癌SGC7901细胞经索拉非尼、DDP单独处理以及两者联合处理后,在不同浓度均能出现细胞生长抑制作用,并且其抑制作用呈时间-剂量依赖效应。与单药组相比,联合作用组对细胞的抑制率明显增高,表现为协同作用(P<0.05)。流式细胞仪检测凋亡的结果显示,经药物处理后细胞凋亡率均较空白对照组升高,两药联合作用的凋亡率要明显高于单药组。单药组及联合用药组对SGC7901细胞ERK的表达无明显影响,但是pERK在单用索拉非尼及联合用药组的表达则降低,以联合用药组尤甚。结论:索拉非尼联合顺铂对胃癌SGC7901细胞有增殖抑制及促凋亡的作用,两药联合表现为协同作用,其机制可能与细胞增殖通路Raf/MEK/ERK的机制有关。

Objective： To investigate the inhibitory effect of sorafenib combined with cisplatin on proliferation of gastric cancer cells and the underlying mechanisms.Methods： SGC7901 cells were treated with sorafenib,cisplatin or sorafenib combined with cisplatin.The cell viability was examined by MTT assay.Apoptosis was detected by flow cytometry.The expression of ERK and pERK were determined by western blot.Results： 1.Sorafenib and cisplatin,used alone or in combination,could significantly inhibit the proliferation of SGC7901 cells time-and dose-dependently.2.The combination of sorafenib and cisplatin markedly sensitized cells to drug-induced apoptosis and suppressed cell proliferation.3.The phosphorylation of ERK was decreased in cells treated with sorafenib.The expression of p-ERK was even dramatically reduced in cells treated with sorafenib combined with cisplatin.Conclusions： The synergistic effect of sorafenib and cisplatin was found in inhibiting cell proliferation and inducing cell apoptosis of gastric cancer cells.Those could partially attribute to the inactivation of Raf/MEK/ERK signaling pathway.