Discordant effect of aspirin and indomethacin on intestinal tumor burden in Apc(Min/+)mice.
Epidemiologic and animal studies indicate that sustained use of non-steroidal anti-inflammatory drugs (NSAIDs) have a chemopreventive effect against the incidence of colorectal neoplasia and subsequent mortality. We previously demonstrated that sulindac significantly reduces intestinal tumor load in Apc(Min/+)mice and the tumor regression was not necessarily correlated with prostaglandin biosynthesis. In the present study, we further investigate the relationship of NSAID treatment and tumorigenesis in the Apc(Min/+)mouse model. We demonstrate that indomethacin (9 ppm) is a very potent chemopreventive agent, reducing tumor load by 85% and significantly inhibiting basal and ex vivo prostaglandin formation (P< 0.006 and P< 0.0001, respectively). Aspirin (400 ppm) has a similar impact on reducing prostaglandin levels, but in contrast to indomethacin, is uneffective in reducing the tumor load. The data indicate a discordance between the impact of different NSAIDs on tumorigenesis in Apc(Min/+)mice.
Chiu
C H
CH
Department of Nutrition, University of Tennessee, Knoxville 37996-1900, USA.
McEntee
M F
MF
Whelan
J
J
D015121:6-Ketoprostaglandin F1 alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D011125:Adenomatous Polyposis Coli / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology*; D001835:Body Weight; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism; D004435:Eating; D007213:Indomethacin / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011448:Prostaglandin Antagonists / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D011448:Prostaglandin Antagonists; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone; D001241:Aspirin; D007213:Indomethacin