摘要
目的:探讨p38丝裂原活化蛋白激酶(p38mitogen-activated protein kinase,p38MAPK)信号转导对幽门螺杆菌(Heli-cobacter pylori,Hp)感染的胃上皮细胞MKN45中环氧合酶(cyclooxygenase-2,COX-2)表达的调控作用,揭示Hp感染引发胃癌的部分机制。方法:采用实时荧光定量-PCR(real-time fluorogentic quantitative-PCR,RFQ-PCR)检测Hp标准株NCTC11637感染对MKN45细胞中COX-2 mRNA表达的影响,Western印迹法检测Hp感染MKN45细胞后p38MAPK信号通路的激活情况;运用p38MAPK特异性抑制剂SB203580阻断p38MAPK信号通路后,观察Hp对MKN45细胞COX-2 mRNA表达的影响。结果:Hp感染MKN45细胞后COX-2mRNA水平明显上调,Hp感染后3、6、9和12h时COX-2 mRNA的表达量分别为正常值的3.0、7.2、5.1和4.3倍,各时间组COX-2 mRNA表达均明显高于对照组(P<0.01)。Hp作用MNK45细胞20min后p38MAPK信号通路被激活,60min时达峰值;而采用p38MAPK特异性抑制剂SB203580阻断p38MAPK信号转导通路后,Hp诱导的COX-2 mRNA表达明显降低(P<0.01)。结论:Hp感染能激活p38MAPK信号通路,通过p38MAPK信号转导上调COX-2的表达,这可能是Hp感染引发胃癌的重要机制之一。
Objective：To investigate the regulatory effect of p38 mitogen-activated protein kinase （p38MAPK） on expression of eyelooxygenase-2 （ COX-2 ） in Helicobacter pylori （Hp） -infected human gastric epithelial MKN45 cells and reveal the mechanism underlying the initiation of gastric cancer induced by Hp. Methods ： The expression of COX-2 mRNA was detected by real-time fluorogenic quantitative polymerase chain reaction （RFQ-PCR） in human gastric epithelial MKN45 cells after infection with standard Hp NCTC11637. The activation of p38MAPK signaling pathway was assessed by Western blotting after Hp infection. The effect of Hp on the expression of COX-2 mRNA in MKN45 cells was observed after blocking p38MAPK signaling pathway with p38MAPK specific inhibitor SB203580. Results：The mRNA expression levels of COX-2 were 3.0-, 7.2-, 5.1- and 4.3-fold of normal value after 3, 6, 9 and 12 h Hp infection （P 〈0.01 ）. The mRNA expression levels of COX-2 were significantly higher than that in the control group at different time points （P 〈 0.01 ）. Hp stimulated the p38MAPK signaling pathway at 20 min after infection and the effect reached the peak at 60 min. The expressions of COX-2 mRNA was significantly decreased after blocking the p38MAPK signaling pathway with p38MAPK specific inhibitor 5B203580 （P 〈 0.01 ）. Conclusion： Hp infection activates the p38MAPK signaling pathway. Upregulation of the expression of COX-2 mRNA in human gastric epithelial cells via p38MAPK signaling pathway may be one of the important mechanisms for the initiation of gastric cancer after Hp infection.
出处
《肿瘤》
CAS
CSCD
北大核心
2009年第2期108-112,共5页
Tumor
基金
国家自然科学基金资助项目(编号:30600844)
上海市重点学科(第3期)资助项目(编号:S30302)
关键词
胃肿瘤
螺杆菌
幽门
环氧化酶2
信号转导
Stomach neoplasms
Helicobacter pylori
Cyelooxygenase 2
Signal transduction
