Helicobacter pylori promotes VEGF expression via the p38 MAPK-mediated COX-2-PGE2 pathway in MKN45 cells
Helicobacter pylori promotes VEGF expression via the p38 MAPK-mediated COX-2-PGE2 pathway in MKN45 cells
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DOI：
10.3892/mmr.2014.2458
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发表时间：
2014-10-01
影响因子：
3.4
通讯作者：
Li, Qi
中科院分区：
文献类型：
--
作者：
Liu, Ningning;Wu, Qiong;Li, Qi
幽门螺杆菌已被认为是胃恶性肿瘤的主要原因。然而，幽门螺旋杆菌感染诱发胃肿瘤的发病机制和分子机制尚不清楚。在本研究中，我们发现在幽门螺杆菌感染的MKN45细胞中，血管内皮生长因子（VEGF）的表达水平升高，而VEGF一直被认为可以促进胃癌血管生成。此外，研究表明p38丝裂原活化蛋白激酶（MAPK）通路通过调节环氧化酶(COX)-2通路调节VEGF的表达。还发现前列腺素E2 （PGE(2)）及其受体EP2/EP4可能介导幽门螺杆菌作用下胃细胞中VEGF的上调。综上所述，在幽门螺杆菌诱导的胃癌细胞中，VEGF的表达受p38 MAPK COX-2-PGE(2)-EP2/EP4通路的调控。这为探讨幽门螺杆菌诱发胃癌的发病机制提供了理论依据。
Helicobacter pylori has been suggested to be the major cause of gastric malignancy. However, the pathogenesis and molecular mechanisms of gastric tumorigenesis induced by H. pylori infection are yet to be elucidated. In the present study, the expression levels of vascular endothelial growth factor (VEGF), which has been suggested to promote angiogenesis in gastric cancer, were found to be elevated in H. pylori-infected MKN45 cells. Furthermore, it was demonstrated that the expression of VEGF was modulated by the p38 mitogen-activated protein kinases (MAPK) pathway via regulation of the cyclooxygenase (COX)-2 pathway. It was also found that prostaglandin E2 (PGE(2)) and its receptor EP2/EP4 may mediate the upregulation of VEGF in gastric cells exposed to H. pylori. In combination, these results suggest that VEGF expression is regulated by the p38 MAPK COX-2-PGE(2)-EP2/EP4 pathway in gastric cancer cells induced by H. pylori. This provides a theoretical basis for the investigation of the pathogenesis of H. pylori-induced gastric cancer.