p38MAPK信号转导通路在COX-2抑制剂联合顺铂诱导人胃癌SGC7901细胞凋亡中的作用机制  

Action Mechanism of p38MAPK Signal Transduction Pathway on Apoptosis of Human Gastric Cancer SGC7901 Cells induced by COX-2 Inhibitor Combined with Cisplatin

作　　者：曹少祥 李华顺 谭海洋[1] 罗良弢 CAO Shao-xiang;LI Hua-shun;TAN Hai-yang;LUO Liang-tao(General surgery Department,first people's Hospital of Tianmen City,Hubei Province,Tianmen 431700;Department of Pathology,first people's Hospital of Tianmen City,Hubei Province,Tianmen 431700)

机构地区：[1]天门市第一人民医院普外科,湖北天门431700 [2]天门市第一人民医院病理科,湖北天门431700

出　　处：《解放军医药杂志》2019年第9期12-17,21,共7页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：湖北省天门市科技攻关项目(20160311202-19)

摘　　要：目的研究p38MAPK信号转导通路在环氧合酶-2(COX-2)抑制剂联合顺铂诱导人胃癌SGC7901细胞凋亡中的作用机制。方法将人胃癌SGC7901细胞根据处理药物不同分为对照组、顺铂组、尼美舒利组和联合组。通过MTT法筛选尼美舒利与顺铂单独作用人胃癌SGC7901细胞的最低有效剂量;Annexin V-FITC/PI染色法进行细胞形态学分析;流式细胞术分析细胞凋亡情况;Western blot方法检测p38、p-p38、p-p53、Bcl-2、Bax及c-caspase-3蛋白表达变化。结果尼美舒利和顺铂对人胃癌SGC7901细胞的最低有效剂量分别为50μmol/L和2.5μmol/L。与单独用药组和对照组相比,二者联合作用后人胃癌SGC7901细胞增殖明显受到抑制(P<0.01),能够显著提高染色阳性细胞百分数(P<0.01),能够显著提高细胞凋亡率(P<0.05),能够促进p38和p53蛋白的磷酸化,抑制Bcl-2蛋白表达,上调Bax及c-caspase-3表达量(P<0.05)。与p38MAPK抑制剂SB203580对人胃癌SGC7901细胞蛋白表达的变化趋势一致。结论尼美舒利联合顺铂能够通过阻断p38MAPK信号转导通路诱导细胞凋亡抑制人胃癌SGC7901细胞增殖,其作用机制可能与促进p38蛋白磷酸化有关。Objective To investigate action mechanism of p38MAPK signal transduction pathway in apoptosis of human gastric cancer SGC7901 cells induced by cyclooxygenase-2(COX-2)inhibitors combined with Cisplatin.Methods Human gastric cancer SGC7901 cells were divided into control group,Cisplatin group,Nimesulide group and Combination group according to different therapeutic drugs.MTT assay was used to screen the minimum effective dosages of Nimesulide and Cisplatin alone affecting human gastric cancer SGC7901 cells.Annexin V-FITC/PI staining was used to analyze cell morphology.Flow cytometry was used to analyze apoptosis condition;Western blot was used to detect expression changes of p38,p-p38,p-p53,b-cell leukemia-lymphoma-2(Bcl-2),Bax and c-caspase-3 proteins.Results The minimum effective dosages of Nimesulide and Cisplatin to human gastric cancer SGC7901 cells were 50μmol/L and 2.5μmol/L respectively.Compared with those by single drug groups and control group,proliferation of human gastric cancer SGC7901 cells was significantly inhibited in combination group(P<0.01),and it could significantly increase percentage of positive staining cells(P<0.01),and it also significantly increased apoptotic rate(P<0.05);combination medication promoted phosphorylation of p38 and p53 proteins,inhibited expression of Bcl-2 protein and up-regulated expressions of Bax and c-caspase-3(P<0.05),and its change trend of protein expression in human gastric cancer SGC7901 cells was consistent with that by p38MAPK inhibitor SB203580.Conclusion Nimesulide combined with Cisplatin may induce apoptosis and inhibit proliferation of human gastric cancer SGC7901 cells by blocking p38MAPK signal transduction pathway.Its mechanism may be related to promotion of p38 protein phosphorylation.

关 键 词：胃肿瘤 环氧化酶-2抑制剂 尼美舒利 顺铂 细胞凋亡 

分 类 号：R735.2[医药卫生—肿瘤]