Cyclooxygenase-2 up-regulates vascular endothelial growth factor via a protein kinase C pathway in non-small cell lung cancer

Background. vascular endothelial growth factor (vegf) expression is up-regulated via a cyclooxygenase-2 (cox-2)-dependent mechanism in non-small cell lung cancer (nsclc),but the specific signaling pathway involved is unclear. our aim was to investigate the signaling pathway that links cox-2 with vegf up-regulation in nsclc. material and methods. cox-2 expression in nsclc samples was detected immunohistochemically,and its association with vegf,microvessel density (mvd),and other clinicopathological characteristics was determined. the effect of cox-2 treatment on the proliferation of nsclc cells (a549,h460 and a431 cell lines) was assessed using the tetrazolium-based mtt method,and vegf expression in tumor cells was evaluated by flow cytometry. cox-2-induced vegf expression in tumor cells was monitored after treatment with inhibitors of protein kinase c (pkc),pka,prostaglandin e2 (pge2),and an activator of pkc. results. cox-2 over-expression correlated with mvd (p = 0.036) and vegf expression (p = 0.001) in nsclc samples,and multivariate analysis demonstrated an association of vegf with cox-2 expression (p = 0.001). exogenously applied cox-2 stimulated the growth of nsclcs,exhibiting ec 50values of 8.95 × 10-3,11.20 × 10 -3,and 11.20 × 10-3 m in a549,h460,and a431 cells,respectively; cox-2 treatment also enhanced tumor-associated vegf expression with similar potency. inhibitors of pkc and pge2attenuated cox-2-induced vegf expression in nlcscs,whereas a pkc activator exerted a potentiating effect. conclusion. cox-2 may contribute to vegf expression in nsclc. pkc and downstream signaling through prostaglandin may be involved in these cox-2 actions. © 2011 luo et al. licensee biomed central ltd.