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Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2.
H Sheng, … , R D Beauchamp, R N DuBois
H Sheng, … , R D Beauchamp, R N DuBois
Published May 1, 1997
Citation Information: J Clin Invest. 1997;99(9):2254-2259. https://doi.org/10.1172/JCI119400.
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Research Article

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

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Abstract

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.

Authors

H Sheng, J Shao, S C Kirkland, P Isakson, R J Coffey, J Morrow, R D Beauchamp, R N DuBois

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