Inhibition of azoxymethane-induced colon carcinogenesis in rats due to JTE-522, a selective cyclooxygenase-2 inhibitor.
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.
Shen
Jun
J
Department of Pathology, Osaka City University Medical School, Osaka 545-8585, Japan.
Wanibuchi
Hideki
H
Salim
Elsayed I
EI
Wei
Min
M
Yamachika
Takesuke
T
Fukushima
Shoji
S
D000284:Administration, Oral; D000821:Animal Feed; D000818:Animals; D001397:Azoxymethane / Q000008:administration & dosage / Q000494:pharmacology; D001557:Benzenesulfonates / Q000494:pharmacology*; D002273:Carcinogens / Q000008:administration & dosage / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000503:physiopathology / Q000517:prevention & control* / Q000662:veterinary; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000473:pathology; D008297:Male; D010080:Oxazoles / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D000096926:Benzenesulfonamides
D001397:Azoxymethane; D001557:Benzenesulfonates; D002273:Carcinogens; D016861:Cyclooxygenase Inhibitors; D010080:Oxazoles; D018809:Proliferating Cell Nuclear Antigen; C110453:4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide; D000096926:Benzenesulfonamides