索拉非尼联合吉西他滨对k-ras基因突变肺癌细胞株的增殖抑制作用及其机制  

Inhibitory effect of sorafenib combined with gemcitabine on human none-small cell lung cancer cells harboring k-ras gene mutation and its mechanism

作　　者：李静[1] 潘跃银[2] 张颖 

机构地区：[1]安徽医科大学附属省立医院干部病房,安徽合肥230001 [2]安徽医科大学第一附属医院肿瘤科,安徽合肥230022 [3]第三附属医院干部病房,安徽合肥230061

出　　处：《中国药理学通报》2014年第3期125-128,共4页Chinese Pharmacological Bulletin

基　　金：安徽省年度科研计划项目(No 09020303042);安徽省年度科研计划项目(No 11070403061)

摘　　要：目的探讨索拉非尼(sorafenib)单药以及联合吉西他滨(gemcitabine)对k-ras基因突变的非小细胞肺癌H460、A549细胞株的抑制作用及相关机制。方法索拉非尼、吉西他滨以及两药联合作用于H460、A549细胞株。MTT法检测增殖抑制作用,流式细胞仪检测对细胞周期的影响,蛋白质印迹法检测p-erk、erk以及bcl-2的变化。结果索拉非尼抑制H460及A549细胞的增殖,联合吉西他滨有协同作用,索拉非尼将H460和A549细胞阻滞于G0/G1期,而吉西他滨将细胞阻滞在S期;吉西他滨单药上调p-erk、bcl-2,索拉非尼单药以及两药联合下调p-erk、bcl-2。结论索拉非尼能抑制k-ras基因突变的H460和A549细胞株的生长,联合吉西他滨有协同作用。Aim To investigate the antiproliferative effects and mechanism of sorafenib alone and combined with gcmcitabine on k-ras gene mutation human non- small cell lung cancer H460 and A549 cells. Methods H460 and A549 cells were exposed to sorafenib, gemcitsbine and in combination of the two. MTT assay was applied to assess the antiproliferative effects. The flow eytometry（ FCM）was used to analyze the alteration d cell cycle. The change d p-erk, erk and bel-2 level was measured by Western blot. Results Sorafenib could inhibit the proliferation d H460 and A549 cells, and combined with gemeitabine,it could generate syn-ergistic effect. Sorsfenib resulted in cell cycle an＇est at Go/G1 phase, whereas gemcitabine arrested st S phase in H460 and A549 cells. Gemcitabine increased the level of p-erk and bcl-2, whereas sorafenib alone and combined with gemcitabine reduced the level of p-erk and bcl-2. Conclusion Sorafenib can inhibit the growth of H460 and A549 cells harboring k-ras gene mutation, and combined with gemcitabine,it generates synergistic effect.

关 键 词：索拉非尼 吉西他滨 肺癌 细胞周期 蛋白印迹 K-RAS 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学] R329.28[医药卫生—基础医学]