AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA
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Sulindac, a nonsteroidal anti-inflammatory drug, has been reported to be effective in suppressing tumor growth through the induction of p21WAF1/cip1 in human, animal models of colon cancer and colon cancer cells. In this study, we treated human breast cancer cell line MCF-7, lung cancer cell line A549 and colon cancer cell line SW620 with sulindac to observe the effects of sulindac in other tissue sites. In all three cell lines, proliferation was significantly inhibited by sulindac after 24 hours of treatment. The apoptosis was induced by sulindac in both lung cancer cells and colon cancer cells but the induction of apoptosis was not observed in the breast cancer cells. To further explore the role of p21WAF1 in these actions, the cell lysate was collected after the treatment of 8, 24 and 48 hours with sulindac. Protein expression was assayed by western blot. As documented previously, p21WAF1 was induced by sulindac in colon cancer cell line. However, p21 was not induced by sulindac in the breast or lung cancer cell lines. Unexpectedly, the suppression of beta-catenin, a key regulator of Wnt-pathway was seen in all the three cell lines with sulindac administration. Subsequently, cyclin D1 and cdk 4 were dramatically suppressed by sulindac. In conclusion, our data demonstrated that the efficiency of sulindac in the inhibition of cell proliferation (other than the induction of apoptosis) may be through the suppression of beta-catenin pathway in human breast and lung cancer cell lines.