Involvement of COX-2/PGE2 Pathway in the Upregulation of MMP-9 Expression in Pancreatic Cancer

COX-2 and MMP-9 have been reported to show an overexpression in pancreatic cancer, and thus an attempt to explore the correlation between them has become a target of this study. Besides, PGE(2), a product of COX-2, was also under research as to whether it is involved in the upregulation of MMP-9 expression by COX-2. Expression of COX-2 and MMP-9 mRNA varied in pancreatic adenocarcinomas, and the mRNA level of COX-2 was correlated positively with MMP-9. Both BxPC-3 and Capan-1 cells had strong expression of COX-2 and MMP-9. MMP-9 expression was downregulated significantly in BxPC-3 and Capan-1 cells after treatment with COX-2 inhibitors or COX-2 siRNA plasmids, and upregulated in BxPC-3 significantly by exogenous TNF-alpha, LPS or PGE(2). The upregulation of MMP-9 by TNF-alpha or LPS was inhibited by COX-2 inhibitor NS398. There was a significant increase in the migration of BxPC-3 cells with TNF-alpha, LPS, or PGE(2) treatment; however, the increase caused by TNF-alpha or LPS was also inhibited remarkably by NS398. Our findings demonstrated that COX-2 upregulates MMP-9 expression in pancreatic cancer, and PGE(2) may be involved in it.