[COX-2 inhibitors in inflammatory bowel disease: friends or foes?].
The cyclooxygenase (COX) is a key enzyme in the conversion of arachidonic acid to prostaglandins. COX-1 is constitutively expressed and is a critical housekeeping gene, whereas COX-2 is rapidly upregulated by growth factors and cytokines and thus responsible for inflammation. COX-2 is frequently overexpressed in colonic adenoma and carcinoma. Specific inhibitors of COX-2 have been shown to induce apoptosis in tumor cells and to inhibit tumor growth in animal models and in humans. Long-standing IBD patients have increased risk of developing colorectal cancer compared to general population. IBD-associated colorectal carcinogenesis is probably promoted by chronic inflammation and closely related to COX-2. In a recent study, powerful chemopreventive ability of selective COX-2 inhibitor was observed in colitis-related colon carcinogenesis in mouse model. But it was reported that even selective COX inhibitors aggravated the DSS-induced colonic inflammation. It is assumed that endogenous PGs are involved in the mucosal defense against DSS-induced colonic ulcerations which are produced by COX-1 at early phase and by COX-2 at late phase. Long-term use of COX-2 inhibitors for the chemoprevention of colitic cancer is needed to define their mechanism of action, that reduce side effects and have specific tumor target.
Park
Young Sook
YS
Department of Internal Medicine, Eulji University School of Medicine, Nowon-Gu, Seoul, Korea. pys1109@eulji.ac.kr
D000818:Animals; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003110:Colonic Neoplasms / Q000175:diagnosis; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D023421:Models, Animal
D052246:Cyclooxygenase 2 Inhibitors; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2