Li Qi, Liu Ningning, Shen Bo, Zhou Lihong, Wang Yan, Wang Yiqin, Sun Jue, Fan Zhongze, Liu Rui Hai
Department of Oncology, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
Cancer Lett. 2009 Jun 8;278(1):97-103. doi: 10.1016/j.canlet.2008.12.032. Epub 2009 Feb 6.
The over-expression of COX-2 (Cyclooxygenase 2) protein has been reported to play a key role in the incidence and development of Helicobacter pylori-associated gastric cancer. The induction of COX-2 in the gastric cancer cells with H. pylori has been demonstrated previously, but little is known about the mechanism. This study reported that the COX-2 mRNA and proteins expression level and the activity of COX-2 promoter increased remarkably with H. pylori stimulation in the MKN45 gastric cancer cells. H. pylori also stimulated phosphorylation of p38MAPK and ATF-2, which is the downstream kinase of p38MAPK. Moreover, the expression levels of COX-2 were suppressed with p38MAPK inhibitor treatment. These results suggest that H. pylori-induced activation of p38MAPK/ATF-2-mediated signal pathway is necessary for the expression of COX-2.
据报道,COX-2(环氧化酶2)蛋白的过度表达在幽门螺杆菌相关胃癌的发生和发展中起关键作用。先前已证明幽门螺杆菌可诱导胃癌细胞中COX-2的产生,但对其机制了解甚少。本研究报道,在MKN45胃癌细胞中,幽门螺杆菌刺激后COX-2 mRNA和蛋白表达水平以及COX-2启动子活性显著增加。幽门螺杆菌还刺激p38MAPK和ATF-2(p38MAPK的下游激酶)的磷酸化。此外,用p38MAPK抑制剂处理可抑制COX-2的表达水平。这些结果表明,幽门螺杆菌诱导的p38MAPK/ATF-2介导的信号通路激活是COX-2表达所必需的。