Introduction.In pancreatic cancer, angiogenesis is an exciting therapeutic target that has been linked to Cyclooxygenase-2 (COX-2) and Vascular Endothelial Growth Factor (VEGF) expression. The relationship of COX-2 and VEGF to endothelial cell (EC) survival and proliferation within the neoplastic environment was investigated in this study.Methods.BxPC-3 or AsPC-1 pancreatic cancer cell lines (COX-2 positive and negative, respectively) were co-cultured with EC for 3-5 days. A 4μm porous membrane, insert system was used to facilitate passage of growth factors but not cells. SC-560 (COX-1 inhibitor), NS398 (COX-2 inhibitor) or VEGF neutralising antibody were added to the lower chamber. EC viability was measured by Giemsa staining and WST assays. PGE2 and VEGF were quantified by ELISA. Significance was calculated using unpaired t test.Results.BxPC-3 co-cultures produced 2.7 fold more PGE2 and 1.5 fold more VEGF than AsPC-1 wells (P<0.01). This was associated with a 2 times greater EC viability in BxPC-3 wells relative to AsPC-1 (P<0.01). PGE2 was reduced to minimal levels in BxPC-3 wells by NS398 but this had no effect on either VEGF production or EC viability. AsPC-1 showed similar patterns but at a proportionally lower level (P<0.01). EC viability was reduced to that of negative control in both cell lines by VEGF neutralising antibody.Conclusion.COX-2 inhibition did not reduce VEGF production or EC viability. However, neutralisation of VEGF did markedly inhibit EC proliferation and survival. Therefore VEGF is not downstream of COX-2 and VEGF inhibitors have an important role in therapies targetting pancreatic cancer angiogenesis.