Suppression of azoxymethane-induced colon cancer development in rats by a cyclooxygenase-1 selective inhibitor, mofezolac.
We demonstrated recently that mofezolac, a cyclooxygenase-1 (COX-1) selective inhibitor, suppresses the development of azoxymethane (AOM)-induced colonic aberrant crypt foci in F344 rats and intestinal polyps in APC1309 mice. In the present study, we therefore investigated the effects of mofezolac on colon cancer development. Male F344 rats were injected subcutaneously with 15 mg/kg body weight of AOM in the back twice at 7-day intervals from 5 weeks of age, and fed a diet containing 600 or 1200 ppm mofezolac for 32 weeks, starting 1 day before the first dosing of AOM. Treatment with 1200 ppm mofezolac significantly reduced the incidence, multiplicity and volume of colon carcinomas to 79%, 2.15 +/- 1.65 and 7.5 +/- 11.8 mm3, respectively, compared with 94%, 3.19 +/- 1.87 and 23.7 +/- 31.2 mm3 in the AOM treatment alone. Administration of 600 ppm mofezolac showed only a slight reduction. No side effects were observed in any of the groups. These results confirm that COX-1, as well as COX-2, contributes to colon carcinogenesis and that mofezolac may be a good chemopreventive agent for human colon cancer.
Niho
Naoko
N
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Tokyo, Japan.
Kitamura
Tomohiro
T
Takahashi
Mami
M
Mutoh
Michihiro
M
Sato
Hidetaka
H
Matsuura
Mamoru
M
Sugimura
Takashi
T
Wakabayashi
Keiji
K
D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D002277:Carcinoma / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D051545:Cyclooxygenase 1 / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000502:physiology; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D007555:Isoxazoles / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344
D052246:Cyclooxygenase 2 Inhibitors; D007555:Isoxazoles; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D001397:Azoxymethane; C054999:mofezolac