ASPIRIN PREVENTS TUMORS IN A MURINE MODEL OF FAMILIAL ADENOMATOUS POLYPOSIS

Background. Both human and murine studies suggest that anti-inflammato ry drugs prevent intestinal neoplasia. The purpose of this study was t o investigate the role of aspirin as a chemopreventive agent for color ectal cancer. Methods, We administered aspirin to the Min/+ mouse, an animal with a germline mutation in Ape, a gene that is essential for n ormal epithelial cell growth and differentiation. Apc mutation increas es cytoplasmic beta-catenin, a regulatory protein associated with the cytoskeleton. Min/+ mice develop multiple intestinal adenomas and exhi bit altered cell growth in the preneoplastic intestinal epithelium. Re sults, Aspirin decreased the rate of tumor formation in Min/+ mice by 44%. Aspirin also normalized enterocyte growth by increasing apoptosis and proliferation in the preneoplastic intestinal mucosa. Finally, as pirin produced a decrease in intracellular beta-catenin levels, sugges ting that modulation of this protein is associated with tumor preventi on. Conclusions, These data confirm a role for aspirin in suppression of Apc-associated intestinal carcinogenesis.