Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells

• Published in: Cancer research (Chicago, Ill.) Ill.), 1998-01, Vol.58 (2), p.362-366
• Main Authors: SHENG, H, SHAO, J, MORROW, J. D, BEAUCHAMP, R. D, DUBOIS, R. N
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Biological and medical sciences; Clone Cells - drug effects; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Dinoprostone - metabolism; Dinoprostone - pharmacology; Dose-Response Relationship, Drug; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunoblotting; Isoenzymes - metabolism; Medical sciences; Membrane Proteins; Mice; Mice, Nude; Neoplasms, Experimental - pathology; Prostaglandin-Endoperoxide Synthases - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Pyrazoles - pharmacology; Stem Cells - drug effects; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Transplantation, Heterologous; Tumor Cells, Cultured - drug effects; Tumors
• ISSN: 0008-5472; 1538-7445

Previously, we have shown that forced expression of prostaglandin endoperoxide synthase-2 [also called cyclooxygenase (COX) 2] leads to inhibition of programmed cell death in intestinal epithelial cells. More recently, we have demonstrated that growth of human colonic cancer xenografts is inhibited by treatment with a highly selective COX-2 inhibitor in tumors that express COX-2 (HCA-7) but not in those that lack COX-2 expression (HCT-116). To explore the biochemical mechanisms involved in these effects, we have evaluated the role of COX-2-derived eicosanoid products on programmed cell death in human colon cancer cells. Here we report that PGE2 treatment of human colon cancer cells leads to increased clonogenicity of HCA-7, but not HCT-116 cells. Treatment with a highly selective COX-2 inhibitor (SC-58125) decreases colony formation in monolayer culture and this growth inhibition was reversed by treatment with PGE2. Additionally, PGE2 inhibits programmed cell death caused by SC-58125 and induces Bcl-2 expression, but did not affect Bcl-x or Bax expression in human colon cancer (HCA-7) cells. Therefore, decreased cell death caused by PGE2 would enhance the tumorigenic potential of intestinal epithelial cells. Thus, these results may help to explain a component of the mechanism by which COX inhibitors prevent colorectal cancer in humans.