Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2

• Published in: The Journal of clinical investigation Vol. 99; no. 9; pp. 2254 - 2259
• Main Authors: Sheng, H, Shao, J, Kirkland, S C, Isakson, P, Coffey, R J, Morrow, J, Beauchamp, R D, DuBois, R N
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.05.1997
• Subjects: Animals; Blotting, Northern; Blotting, Western; Cell Division; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - enzymology; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Cyclooxygenase Inhibitors - therapeutic use; Humans; Isoenzymes - genetics; Isoenzymes - immunology; Isoenzymes - metabolism; Membrane Proteins; Mice; Mice, Nude; Prostaglandin-Endoperoxide Synthases - genetics; Prostaglandin-Endoperoxide Synthases - immunology; Prostaglandin-Endoperoxide Synthases - metabolism; Prostaglandins - immunology; Prostaglandins - metabolism; Pyrazoles - pharmacology; Pyrazoles - therapeutic use; RNA - analysis; RNA - metabolism; Transplantation, Heterologous; Tumor Cells, Cultured
• ISSN: 0021-9738
• DOI: 10.1172/jci119400

A considerable amount of evidence collected from several different experimental systems indicates that cyclooxygenase-2 (COX-2) may play a role in colorectal tumorigenesis. Large epidemiologic studies have shown a 40-50% reduction in mortality from colorectal cancer in persons taking aspirin or other nonsteroidal antiinflammatory drugs on a regular basis. One property shared by all of these drugs is their ability to inhibit COX, a key enzyme in the conversion of arachidonic acid to prostaglandins. Two isoforms of COX have been characterized, COX-1 and COX-2. COX-2 is expressed at high levels in intestinal tumors in humans and rodents. In this study, we selected two transformed human colon cancer cell lines for studies on the role of COX-2 in intestinal tumorigenesis. We evaluated HCA-7 cells which express high levels of COX-2 protein constitutively and HCT-116 cells which lack COX-2 protein. Treatment of nude mice implanted with HCA-7 cells with a selective COX-2 inhibitor (SC-58125), reduced tumor formation by 85-90%. SC-58125 also inhibited colony formation of cultured HCA-7 cells. Conversely, SC-58125 had no effect on HCT-116 implants in nude mice or colony formation in culture. Here we provide evidence that there may be a direct link between inhibition of intestinal cancer growth and selective inhibition of the COX-2 pathway.