Suppressive effects of nimesulide, a selective inhibitor of cyclooxygenase-2, on azoxymethane-induced colon carcinogenesis in mice.
The effects of nimesulide, a selective inhibitor of cyclooxygenase-2 (COX-2) on azoxymethane (AOM)-induced colon carcinogenesis were investigated in mice. AOM at a dose of 10 mg/kg body wt was administered to male ICR mice once a week for 6 weeks. The animals were fed on AIN-76A powder diet containing nimesulide at doses of 200 or 400 p.p.m., starting the day before the first carcinogen treatment until the end of the experiment, at week 30. Administration of nimesulide reduced the incidence of colon carcinomas to 32 and 25% for the AOM + 200 and 400 p.p.m. nimesulide groups, respectively, compared with the AOM + basal diet group (50%). Multiplicities of colon carcinomas in the 200 and 400 p.p.m. nimesulide-treated groups were 0.70 +/- 0.28 and 0.35 +/- 0.11, respectively, being significantly smaller than the AOM alone value (1.79 +/- 0.47). The sizes of the colon carcinomas in the nimesulide-treated groups were also decreased. No significant influence on liver and lung tumor development was apparent. Thus, nimesulide exerted a suppressive effect on AOM-induced colon carcinogenesis in mice.
Fukutake
M
M
Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan.
Nakatsugi
S
S
Isoi
T
T
Takahashi
M
M
Ohta
T
T
Mamiya
S
S
Taniguchi
Y
Y
Sato
H
H
Fukuda
K
K
Sugimura
T
T
Wakabayashi
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001397:Azoxymethane / Q000633:toxicity; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D007527:Isoenzymes / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D001397:Azoxymethane; C012655:nimesulide