Department of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Prostaglandins Other Lipid Mediat. 2009 Nov;90(1-2):31-6. doi: 10.1016/j.prostaglandins.2009.07.003. Epub 2009 Jul 30.
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(1alpha), 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(1alpha) 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.
越来越多的证据表明环氧化酶-2（COX-2）和前列腺素 E2（PGE2）在结肠癌的发生中可能起着重要作用。因此，阻断这一途径可能是结肠癌化学预防的一种合适策略。最近的临床研究表明，COX-2 抑制剂由于抑制前列环素（PGI2）而引起不良的心血管效应。为了验证我们的假设，即通过 E-前列腺素（EP）受体抑制 PGE2 信号可能提供比 COX-2 抑制更安全的心血管特征，我们分析了在人脐静脉内皮细胞（HUVEC）中用细胞因子刺激时，6-酮前列腺素 F1α（PGI2 的水合形式）和 PGI2 合酶的表达，这些细胞用 EP1 受体拮抗剂 ONO-8711 或 COX-2 抑制剂塞来昔布处理。ONO-8711 没有抑制 6-酮前列腺素 F1α的产生和 PGIS 的表达，而塞来昔布在 HUVEC 中则有抑制作用。ONO-8711 还抑制了细胞因子诱导的 HUVEC 中组织因子的表达。这些结果表明，ONO-8711 可能是一种更安全的化学预防剂，与心血管事件有关。
