Inhibition of prostaglandin E 2 signaling through the EP 1 receptor does not affect prostacyclin production in human endothelial cells

Abstract

Accumulating evidence suggests that cyclooxygenase-2 (COX-2) and prostaglandin E 2 (PGE 2) may play an important role in colon carcinogenesis. Thus, blockage of this pathway may be a suitable strategy for colon cancer chemoprevention. Recent clinical studies suggest that COX-2 inhibitors cause adverse cardiovascular effects due to prostacyclin (PGI 2) inhibition. To test our hypothesis that inhibition of PGE 2 signaling through E-prostanoid (EP) receptors may offer a safer cardiovascular profile than COX-2 inhibition, we analyzed expression of 6-keto PGF 1α, a hydrated form of PGI 2 and PGI 2 synthase, which was stimulated with cytokines in human umbilical vein endothelial cells (HUVECs) treated with the EP 1 receptor antagonist ONO-8711 or the COX-2 inhibitor celecoxib. ONO-8711 did not inhibit both 6-keto PGF 1α production and PGIS expression, whereas celecoxib did in HUVECs. ONO-8711 also inhibited cytokine-induced tissue factor expression in HUVECs. These results suggest that ONO-8711 may be a safer chemopreventive agent with respect to cardiovascular events.