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

Hongmiao Sheng, Jinyi Shao, Susan C. Kirkland, Peter Isakson, Robert J. Coffey, Jason Morrow, R. Daniel Beaucnamp, Raymond N. DuBois

Research output: Contribution to journalArticle

669 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2254-2259
Number of pages6
JournalJournal of Clinical Investigation
Volume99
Issue number9
DOIs
StatePublished - May 1 1997

Keywords

  • chemoprevention
  • colon cancer
  • cyclooxygenase-2
  • nonsteroidal antiinflammatory drug

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2'. Together they form a unique fingerprint.

  • Cite this

    Sheng, H., Shao, J., Kirkland, S. C., Isakson, P., Coffey, R. J., Morrow, J., Beaucnamp, R. D., & DuBois, R. N. (1997). Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. Journal of Clinical Investigation, 99(9), 2254-2259. https://doi.org/10.1172/JCI119400