MODULATION OF APOPTOSIS AND BCL-2 EXPRESSION BY PROSTAGLANDIN E-2 IN HUMAN COLON-CANCER CELLS

Previously, we have shown that forced expression of prostaglandin endo peroxide synthase-2 [also called cyclooxygenase (COX) 2] leads to inhi bition of programmed cell death in intestinal epithelial cells, More r ecently, we have demonstrated that growth of human colonic cancer xeno grafts is inhibited by treatment with a highly selective COX-2 inhibit or in tumors that express COX-2 (HCA-7) but not in those that lack COX -2 expression (HCT-116). To explore the biochemical mechanisms involve d in these effects, we have evaluated the role of COX-2-derived eicosa noid products on programmed cell death in human colon cancer cells, He re we report that PGE(2) treatment of human colon cancer cells leads t o increased clonogenicity of HCA-7, but not HCT-116 cells, Treatment w ith a highly selective COX-2 inhibitor (SC-58125) decreases colony for mation in monolayer culture and this growth inhibition was reversed by treatment with PGE(2). Additionally, PGE(2) inhibits programmed cell death caused by SC-58125 and induces Bcl-2 expression, but did not aff ect Bcl-x or Bax expression in human colon cancer (HCA-7) cells, There fore, decreased cell death caused by PGE(2) would enhance the tumorige nic potential of intestinal epithelial cells, Thus, these results may help to explain a component of the mechanism by which COX inhibitors p revent colorectal cancer in humans.