Helicobacter pylori-induced VEGF expression in human gastric cancer MKN45 cells mediated by COX-2 / 中国癌症杂志

ABSTRACT

Background and purpose: Vascular endothelial growth factor (VEGF) is an important proangiogenic factor, and Helicobacter pylori (H. pylori) infection-induced gastric over-expression of VEGF is an important factor of gastric cancer growth and metastasis, but its expression mechanism is not clear. Cyclooxygenase-2 (COX-2) is a rapid response protein, which is closely related to the occurrence and development of gastric cancer. Our study was to investigate the effect of COX-2 on H. pylori-induced VEGF expression in human gastric cancer cells, and to reveal part of the mechanism of gastric cancer growth and metastasis promoted by H. pylori infection. Methods:The expression ofVEGF mRNA in human gastric epithelial cells (MKN45) infected by standard H. pylori NCTC 11637 and the expression of COX-2 protein were evaluated by real-time fluorogenic quantitative polymerase chain reaction (RFQ-PCR) and assayed by Western blot. After inhibiting COX-2 expression with COX-2 specific inhibitor NS398 (50 μmol/L), VEGF mRNA expression induced by H. pylori in human gastric cancer MKN45 cells was evaluated by RFQ-PCR. Results: H. pylori significantly stimulated the expression ofVEGF mRNA in MKN45 cell line. Compared with control MKN45 cells; VEGF mRNA had 2.33 fold up-regulation after 6 h (P<0.05); and had 5.69 and 5.04 fold upregulation respectively after 12 and 24 h (P<0.01).When MKN45 cells were infected with H. pylori for 24 h, COX-2 protein expression also increased significantly (P<0.01), and after inhibiting the COX-2 expression with COX-2 specific inhibitor NS398, H. pylori-induced VEGF mRNA expression was significantly reduced. Conclusion: H. pylori could induce the expression of COX-2 and VEGF in human gastric cancer cells, and could enhance VEGF expression by COX-2 pathway, which might be one of the important mechanisms of gastric cancer growth and metastasis promoted by H. pylori infection.