ERK通路对胃癌细胞顺铂敏感性的调节作用

Regulatory role of the extracellular signal-regulated kinase signaling pathway in sensitivity of gastric cancer cells to cis-platinum

目的:研究在人胃癌细胞中,细胞外信号调节蛋白激酶(extracellular signal-regulated kinase,ERK)通路对人胃癌细胞顺铂敏感性的影响.方法:采用MTT法测定顺铂对两种胃癌细胞MGC-803、BGC-823的增殖抑制影响,测定PD98059作用BGC-823细胞后顺铂对细胞的增殖抑制影响.Western blot方法检测MGC-803、BGC-823细胞中谷胱甘肽-S-转移酶π(glutathione S-transferases π,GST-π)蛋白的表达;及PD98059作用BGC-823细胞24h后BGC-823细胞中p-ERK、GST-π蛋白的表达.结果:顺铂作用两种胃癌细胞72h后,MGC-803,BGC-823细胞的IC50值分别为0.71和1.21mg/L,且MGC-803细胞的增殖率明显低于BGC-823细胞的增殖率(P<0.05).MGC-803细胞顺铂的敏感性高于BGC-823细胞.MGC-803细胞不表达GST-π蛋白,BGC-823细胞强表达GST-π蛋白.20μmol/LPD98059作用BGC-823细胞24h后,p-ERK蛋白表达明显下调,GST-π蛋白表达亦明显下调.20μmol/LPD98059作用BGC-823细胞24h后,加入顺铂培养48h,BGC-823+PD98059组增殖率明显低于对照组,BGC-823细胞对顺铂的敏感性明显增强.结论:下调胃癌细胞GST-π蛋白的表达可增强其对顺铂的敏感性;抑制胃癌细胞中ERK通路的活化,可以降低其细胞内GST-π蛋白表达;ERK通路通过调节人胃癌细胞GST-π基因表达影响其对顺铂的敏感性.

AIM：To investigate the regulatory role of the extracellular signal-regulated kinase （ERK） signaling pathway in sensitivity of gastric cancer cells to cis-platinum （CDDP）.METHODS：Gastric cancer cells （MGC-803 and BGC-823） were first treated with CDDP for 72 hours.Twenty-four hours after culture with PD98059,cells were treated with CDDP for 48 hours.Cell proliferation was then measured by methyl thiazolyl tetrazolium （MTT） assay.The expression of glutathione S-transferases π （GST-π）and p-ERK was detected by Western blot. RESULTS： The half maximal inhibitory concentration （IC50） of CDDP for 72 hours in MGC-803 and BGC-823 cells were 0.71 and 1.21 mg/L, respectively. The proliferation rate of MGC-803 cells was significantly lower than that of BGC-823 ceils （P 〈 0.05）. MGC-803 cells did not express GST-π, while BGC-823 cells highly expressed GST-π. After PD98059 treatment for 24 h, the expression levels of p-ERK and GST-π significantly decreased in BGC-823 cells, and BGC-823 cells became more sensitive to CDDP. CONCLUSION： Inhibition of the ERK signaling pathway may enhance the sensitivity of gastric cancer cells to CDDP, which is induced by downregulation of GST-π expression.