Effect of aspirin on cell proliferation and differentiation of colon adenocarcinoma Caco-2 cells.

Several lines of evidence suggest that long-term treatment with non-steroidal anti-inflammatory drugs may reduce the risk of colon cancer and the size and number of colonic polyps in patients with familial adenomatous polyposis. Aspirin has also been shown to inhibit cell proliferation in human tumor cell lines and to induce apoptosis in colonic mucosa of familial polyposis patients. To elucidate the molecular mechanisms of the antiproliferative action of aspirin, we studied the effects of aspirin on cell growth and differentiation of the human colon carcinoma Caco-2 cell line. These cells represent a useful tool for studying the mechanisms involved in the regulation of cell growth and differentiation of intestinal epithelial cells since they spontaneously differentiate into polarized cells, expressing brush border enzymes. We show in this study that aspirin (0.1-10 mM) induces a profound inhibition of cell replication as assessed either by cell counts or thymidine incorporation. Moreover, aspirin concentrations of 5 and 10 mM induce apoptosis, whereas concentrations of 1 and 2 mM do not. The inhibition of growth is associated with a dose-dependent reduction in insulin-like growth factor II mRNA expression and with an increase in sucrase activity (a brush border enzyme) and apolipoprotein A-I mRNA expression, 2 specific markers of the differentiative status of this cell line. Our data thus show that aspirin-dependent inhibition of cell growth is associated with the enterocyte-like differentiation of Caco-2 cells.