The role of COX-2 in intestinal cancer

Ann N Y Acad Sci. 1999:889:72-83. doi: 10.1111/j.1749-6632.1999.tb08725.x.

Abstract

Cyclooxygenase (COX), the key regulatory enzyme for prostaglandin synthesis is transcribed from two distinct genes. COX-1 is expressed constitutively in most tissues, and COX-2 is induced by a wide variety of stimuli and was initially identified as an immediate-early growth response gene. In addition, COX-2 expression is markedly increased in 85-90% of human colorectal adenocarcinomas, whereas COX-1 levels remain unchanged. Several epidemiological studies have reported a 40-50% reduction in the risk of developing colorectal cancer in persons who chronically take such nonsteroidal anti-inflammatory drugs (NSAIDs) as aspirin, which are classic inhibitors of cyclooxygenase. Genetic evidence also supports a role for COX-2, since mice null for COX-2 have an 86% reduction in tumor multiplicity in a background containing a mutated APC allele. These results strongly suggest that COX-2 contributes to the development of intestinal tumors and that inhibition of COX is chemo-preventative.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Aspirin / pharmacology
  • Aspirin / therapeutic use
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • Cyclooxygenase Inhibitors / therapeutic use
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Humans
  • Intestinal Neoplasms / enzymology*
  • Intestinal Neoplasms / etiology
  • Intestinal Neoplasms / genetics
  • Intestinal Neoplasms / prevention & control
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Isoenzymes / pharmacology
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Prostaglandin-Endoperoxide Synthases / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Aspirin