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-st eroidal anti-inflammatory drugs may reduce the risk of colon cancer an d the size and number of colonic polyps in patients with familial aden omatous polyposis. Aspirin has also been shown to inhibit cell prolife ration in human tumor cell lines and to induce apoptosis in colonic mu cosa of familial polyposis patients. To elucidate the molecular mechan isms of the antiproliferative action of aspirin, we studied the effect s of aspirin on cell growth and differentiation of the human colon car cinoma Caco-2 cell line. These cells represent a useful tool for study ing the mechanisms involved in the regulation of cell growth and diffe rentiation of intestinal epithelial cells since they spontaneously dif ferentiate into polarized cells, expressing brush border enzymes. We s how in this study that aspirin (0.1-10 mM) induces a profound inhibiti on 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-li ke growth factor II mRNA expression and with an increase in sucrase ac tivity (a brush border enzyme) and apolipoprotein A-I mRNA expression, 2 specific markers of the differentiative status of this cell line. O ur data thus show that aspirin-dependent inhibition of cell growth is associated with the enterocyte-like differentiation of Caco-2 cells. ( C) 1997 Wiley-Liss, Inc.