Chemopreventive efficacy of sulindac sulfone against colon cancer depends on time of administration during carcinogenic process.

摘要: Epidemiological and model studies with laboratory animals have provided evidence that nonsteroidal anti-inflammatory drugs reduce the risk of colon cancer. Sulindac, a drug, has been shown to inhibit azoxymethane (AOM)-induced carcinogenesis in rats when administered continuously before, during, after carcinogen treatment (initiation postinitiation periods) or given beginning 14 weeks administration (promotion/ progression stage). The present study was designed investigate chemopreventive efficacy sulindac sulfone (exisulind), metabolite sulindac, during promotion/progression stage comparison effect initiation periods. We also studied modulating exisulind on colonic tumor apoptosis. At 5 age, groups male F344 were fed diets containing 0%, 0.06%, 0.12% exisulind. 7 injected s.c. AOM (15 mg/kg body weight, once weekly for 2 weeks). Animals intended receiving 0% switched an experimental diet at second treatment. All remained their respective dietary regimens until termination study, 50 injection. Colon tumors evaluated histopathologically type. Administration 0.06% periods significantly inhibited incidence multiplicity invasive and/or noninvasive adenocarcinomas colon. inhibition tumorigenesis by associated significant retardation weight gain shortly increased apoptosis tumors. In contrast, higher dose (0.12%) had only minimal effects tumors, suggesting early administration, but not late may be required this drug.