摘要
目的探讨在肠癌RKO细胞中,MAPK/ERK特异性抑制剂PD98059对奥沙利铂药物敏感性的影响及谷胱甘肽-S-转移酶π(GST-π)在这一过程中的作用。方法采用MTT法测定奥沙利铂和(或)PD98059处理后对人肠癌RKO细胞的增殖抑制影响;Western-blot方法检测PD98059作用人肠癌RKO细胞24 h后,RKO细胞中p-ERK及GST-π蛋白的表达。结果奥沙利铂作用人肠癌RKO细胞24、48和72 h,IC50值分别为38.72、23.41、10.81μg/ml,20μmol/L PD98059预处理RKO细胞24 h后,再加入奥沙利铂培养24、48和72 h,联合用药组细胞增殖率明显低于对照组,RKO细胞对奥沙利铂的药物敏感性显著增强。20μmol/L PD98059作用RKO细胞24 h后,p-ERK蛋白表达明显下调,GST-π蛋白表达亦明显下调。结论 PD98059通过有效抑制ERK通路,进一步下调人肠癌RKO细胞内GST-π的表达,增强RKO对奥沙利铂的药物敏感性。
Objective To investigate the effects of MAPK/ERK specific inhibitor PD98059 on oxaliplatin-treated human colorectal cancer RKO cells and the potential mechanism.Methods Cell proliferation was assessed by MTT assay after treated by oxaliplatin and/or PD98059 in human colorectal cancer RKO cells.Western-blot was used to detect the expressions of p-ERK and glutathione S-transferasesπ(GST-π) in human colorectal cancer RKO cells after treatment of PD98059.Results The IC50 of RKO cells treated by oxaliplatin for 24,48 and 72 hours were 38.72 μg/ml,23.41 μg/ml and 10.81 μg/ml,respectively.After the treatment of 20 μmol/L PD98059,RKO cell line became more sensitive to oxaliplatin.The expression of p-ERK and GST-π were significantly decreased by 20 μmol/L PD98059 treatment after 24 h in RKO cell line.Conclusions ERK signaling pathway,which effective inhibited by PD98059(20 μmol/L) may be one of the important regulations to the drug-sensitivity of human colorectal cancer RKO cells to oxaliplatin,which is induced by controlling the GST-π gene expression.
出处
《中华临床医师杂志（电子版）》
CAS
2011年第23期6957-6960,共4页
Chinese Journal of Clinicians(Electronic Edition)
基金
国家自然科学基金(30901736)
辽宁省教育厅资助科研项目(L2010641)
