Discordant effect of aspirin and indomethacin on intestinal tumor burden in Apc(Min/+) mice

Epidemiologic and animal studies indicate that sustained use of non-steroid al anti-inflammatory drugs (NSAIDs) have a chemopreventive effect against t he incidence of colorectal neoplasia and subsequent mortality. We previousl y demonstrated that sulindac significantly reduces intestinal tumor load in Apc(Min/+) mice and the tumor regression was not necessarily correlated wi th prostaglandin biosynthesis. In the present study, we further investigate the relationship of NSAID treatment and tumorigenesis in the Apc(Min/+) mo use model. We demonstrate that indomethacin (9 ppm) is a very potent chemop reventive agent, reducing tumor load by 85% and significantly inhibiting ba sal and ex vivo prostaglandin formation (P < 0.006 and P < 0.0001, respecti vely). Aspirin (400 ppm) has a similar impact on reducing prostaglandin lev els, but in contrast to indomethacin, is uneffective in reducing the tumor load. The data indicate a discordance between the impact of different NSAID s on tumorigenesis in Apc(Min/+) mice. (C) 2000 Harcourt Publishers Ltd.