The effect of non-steroidal anti-inflammatory drugs on human colorectal cancer cells: evidence of different mechanisms of action

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit proliferation and in duce apoptosis in human colorectal cancer cells in vitro. It remains unclea r whether individual NSAIDs act by cyclooxygenase-2 (COX-2) inhibition and how NSAIDs exert their antiproliferative effects. We investigated the effec ts of NS-398 (a selective COX-2 inhibitor), indomethacin (a non-selective C OX inhibitor) and aspirin on four human colorectal cancer cell lines (HT29. Fu, HCA-7, SW480 and HCT116). NS-398 completely inhibited proliferation, in duced G1 arrest and promoted apoptosis in COX-2-expressing cells (HT29.Fu a nd HCA-7). However, indomethacin had similar effects on all cells, regardle ss of COX-2 expression. NS-398 also had anti-proliferative activity on COX- 2-negative cell lines (SW480 and HCT116). Aspirin inhibited proliferation o f all cell lines but did not induce apoptosis. Indomethacin decreased beta- catenin protein expression in all cells (unlike NS-398 or aspirin). NSAIDs act on human colorectal cancer cells via different mechanisms. Decreased be ta-catenin protein expression may mediate the anti-proliferative effects of indomethacin. (C) 2000 Elsevier Science Ltd. All rights reserved.