Inhibition of azoxymethane-induced colon carcinogenesis in rats due to JTE-522, a selective cyclooxygenase-2 inhibitor.
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Date
2004-07-18
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Abstract
Prostaglandin E2, which is produced by cyclooxygenase (COX) during arachidonic acid metabolism, is considered to be related to colon carcinogenesis and selective COX-2 inhibitors may be effective for chemoprevention without the adverse side effects of non-selective, nonsteroid anti-inflammatory drugs. Therefore, the influence of JTE-522 (4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzensulfonamide), a selective COX-2 inhibitor, was examined in azoxymethane(AOM)-induced rat colon carcinogenesis. A total of 40 male F344 rats were randomly divided into two groups. Group 1 received diet containing 0.015% JTE-522 and group 2 the normal diet without supplement as a control group; one week later, all rats were administered axozymethane (AOM) s.c. at a dose of 15 mg/kg body weight once a week for 3 successive weeks. At the termination of the experiment (30 weeks after the start), the multiplicity of colon cancer in group 1 was significantly less than that of group 2. The proliferating cell nuclear antigen (PCNA) indices for non-neoplastic cells of the colon mucosa in group 1 were also lower. These data thus suggest that JTE-522 has chemopreventive potential against colon carcinogenesis with decrease of mucosal cell proliferation in rats.
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Asian Pacific Journal of Cancer Prevention.
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Shen J, Wanibuchi H, Salim EI, Wei M, Yamachika T, Fukushima S. Inhibition of azoxymethane-induced colon carcinogenesis in rats due to JTE-522, a selective cyclooxygenase-2 inhibitor. Asian Pacific Journal of Cancer Prevention. 2004 Jul-Sep; 5(3): 253-8