Combined therapy with COX-2 inhibitor and 20-HETE inhibitor reduces tumor growth and the adverse effects of ischemic stroke associated with COX-2 inhibition.

Combined therapy with COX-2 inhibitor and 20-HETE inhibitor reduces tumor growth and the adverse effects of ischemic stroke associated with COX-2 inhibition. Am J Physiol Regul Integr Comp Physiol. 2014 Jul 2; Authors: Zhang Y, Hoda MN, Zheng X, Li W, Luo P, Maddipati KR, Seki T, Ergul A, Wang MH Abstract 20-Hydroxyeicosatetraenoic acid (20-HETE), Cyp4a-derived eicosanoid, is a lipid mediator that promotes tumor growth as well as causing detrimental effects in cerebral circulation. We determined whether concurrent inhibition of cyclooxygenase-2 (COX-2) and 20-HETE affects colon tumor growth and ischemic stroke outcomes. The expression of Cyp4a and COXs and production of 20-HETE and PGE2 were determined in murine colon carcinoma (MC38) cells. We then examined the effects of combined treatment with rofecoxib, a potent COX-2 inhibitor, and HET0016, a potent Cyp4a inhibitor, on the growth and proliferation of MC38 cells. Subsequently, we tested the effects of HET0016 plus rofecoxib in MC38 tumor and ischemic stroke models. Cyp4a and COXs are highly expressed in MC38 cells. Respectively, HET0016 and rofecoxib inhibited 20-HETE and PGE2 formation in MC38 cells. Moreover, rofecoxib combined with HET0016 had greater inhibitory effects on the growth and proliferation of MC38 cells than did rofecoxib alone. Importantly, rofecoxib combined with HET0016 provided greater inhibition on tumor growth than did rofecoxib alone in MC38 tumor-bearing mi...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - Category: Physiology Authors: Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research