Sulindac and a cyclooxygenase-2 inhibitor, etodolac, increase APC mRNA in the colon of rats treated with azoxymethane

Background-Non-steroidal anti-inflammatory drugs (NSAIDs) have been reporte d to protect against the development of colon cancer. However, the mechanis m(s) by which NSAIDs exert their effects is not clear. Aims-The aim of this study was to examine the effects of NSAIDs on mRNA exp ression of tumour suppressor adenomatous polyposis coli (AFC) gene in rat c olon mucosa. Methods-Starting at six weeks of age, three groups of rats (groups 1, 2, an d 3) were treated with azoxymethane (AOM), a colon specific carcinogen, and another three groups (groups 4, 5, and 6) were not given AOM. Groups 2 and 3 were given 10 mg/kg of sulindac or etodolac, respectively, three times w eekly during the experiment. Groups 4 and 5 were also given sulindac or eto dolac, respectively, in the same manner as in groups 2 and 3. Group 6 (untr eated control) was not given any agent (AOM or NSAIDs). At 10 weeks of age, preneoplastic lesions (aberrant crypt foci (ACF)) induced by AOM in the co lon were counted, and the level of expression of ATG mRNA in the colonic mu cosa was estimated by the reverse transcription-competitive polymerase chai n reaction method and northern blot analysis. Results-Mean occurrence of ACF in rats in groups 2 and 3 was reduced to app roximately 50% of that in group 1. The level of APC mRNA expression in grou p 1 (AOM alone) was lower than that in group 6 (untreated control) (p<0.05) ; however, levels of APC mRNA expression in groups 2, 3, 4, and 5, to which NSAIDs had been administered, were significantly increased compared with l evels in groups 1 and 6 (p<0.01). Conclusions-Both sulindac and etodolac reduced the occurrence of ACF and in duced an increase in APC mRNA in rat colon mucosa.