MAPK/ERK通路影响人胃癌细胞对奥沙利铂敏感性的机制研究  

The mechanism of MAPK/ERK signaling pathway in sensitivity of human gastric cancer cells to oxaliplatin

作　　者：张晔[1] 徐玲[1] 刘云鹏[1] 曲秀娟[1] 杨向红[2] 侯科佐[1] 滕月娥[1] 张敬东[1] 

机构地区：[1]中国医科大学附属第一医院肿瘤内科,辽宁沈阳110001 [2]中国医科大学附属盛京医院实验病理学研究室,辽宁沈阳110004

出　　处：《现代肿瘤医学》2013年第3期456-458,共3页Journal of Modern Oncology

基　　金：国家自然科学基金资助项目(No.81270036;30901736);辽宁省教育厅实验室项目(No.LS2010169);辽宁省高等学校杰出青年学者成长计划项目(No.LJQ2011082)

摘　　要：目的:探讨MAPK/ERK通路对人胃癌细胞奥沙利铂敏感性的影响,并进一步探讨其机制。方法:采用MTT法测定奥沙利铂对人胃癌BGC823和SGC7901细胞的增殖抑制影响;MAPK/ERK特异性抑制剂PD98059预处理上述两种细胞后,测定奥沙利铂的药物敏感性。Western blot方法检测胃癌细胞中p-ERK、ERK及谷胱甘肽-S-转移酶π(glutathione S-transferasesπ,GST-π)蛋白表达。应用SPSS 13.0软件包进行统计学分析。结果:1mg/L-100mg/L奥沙利铂分别作用BGC823和SGC7901细胞,48h的IC50分别为24.26mg/L和18.44 mg/L;20μmol/L的PD98059预处理BGC823和SGC7901细胞,再加入奥沙利铂继续培养48h,IC50分别降至12.42mg/L和7.97mg/L,表明对奥沙利铂的敏感性显著提高。进一步检测发现PD98059处理BGC823和SGC7901细胞24h后,p-ERK蛋白表达明显下调,GST-π蛋白亦显著下调。结论:PD98059通过抑制MAPK/ERK通路,下调GST-π蛋白表达,显著提高人胃癌细胞对奥沙利铂的药物敏感性。Objective：To explore the effect of the mitogen- activated protein kinase （MAPK）/extracellular regu- lated kinase （ERK） signaling pathway on oxaliplatin- treated human gastric cancer cells and the potential mecha- nism. Methods： Cell proliferation was assessed by MTY assay after treated by oxaliplatin and/or PD98059 （ the selec- tive MAPK/ERK pathway inhibitor） in BGC823 and SGC7901 cells. The expressions of p - ERK and GST - π pro- teins were detected by western blot. All experimental data were analyzed with by SPSS （13.0 soft）. Results：The IC50 values of BGC823 and SGC7901 cells treated by oxaliplatin for 48 hours were 24.26 mg/L and 18.44 mg/L,respec- tively. After the pretreatment of 20umol/L PI）98059, BGC823 and SGC7901 cell lines became more sensitive to oxali- platin, the ICs0 values of 48 hours were 12.42 and 7.97 mg/L, respectively. The expressions of p - ERK and GST - π were significantly decreased by 20 umol/L PD98059 treatment after 24h in BGC823 and SGC7901 cell lines. Conclu- tion：Inhibition of the MAPK/ERK signaling pathway by PD98059 may enhance the sensitivity of gastric cancer cells to oxaliplatin,which is induced by downregulation of GST-w expression.

关 键 词：胃癌 奥沙利铂 细胞外信号调节蛋白激酶 谷胱甘肽-S-转移酶Π 

分 类 号：R373.21[医药卫生—病原生物学]