Cyclooxygenase-2 induces angiogenesis in pancreatic cancer mediated by prostaglandin E 2 .

The purpose of the present study was to elucidate the effects of cyclooxygenase 2 (COX-2) on the expression of vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2 ) in pancreatic cancer in vitro and in vivo , and to clarify the potential mechanism of COX-2-induced angiogenesis of pancreatic cancer. The study analysis was conducted in the pancreatic cancer PC-3 cell line. The expression of COX-2 and VEGF in human pancreatic cancer tissue was analyzed by immunohistochemistry. Angiogenesis was detected using immunohistochemistry with anti-collagen IV antibodies, and was calculated according to the microvascular density (MVD). In vitro analysis was performed using ELISA or radioimmunoassay (RIA). The effect of exogenous PGE2 on the downregulation of VEGF by Celebrex was also assessed. In vivo analysis was performed using western blotting or RIA. Concurrently, MVD was also investigated in nude mice using immunohistochemistry with anti-collagen IV antibodies. COX-2 was overexpressed in pancreatic cancer tissues, with an overall positive rate of 87.5%. There was a positive association between the expression of COX-2 and MVD. The in vitro study indicated that Celebrex suppressed the expression of VEGF and PGE2 in PC-3 cells in a dose- and time-dependent manner, while exogenous PGE2 rescued the expression of VEGF, which was suppressed by Celebrex, in a dose-dependent manner. The in vivo study revealed that the administration of Celebrex to xenograft nude mice significantly inhibited the expression of VEGF and PGE2 . These data provide evidence that PGE2 may be an important mediator between COX-2 and VEGF expression in the process of angiogenesis in pancreatic cancer.