Role of cyclooxygenase-2 in colorectal cancer

Cancer Metastasis Rev. Jan-Jun 2004;23(1-2):63-75. doi: 10.1023/a:1025863029529.

Abstract

Cyclooxygenase-2 (COX-2) is an inducible enzyme that regulates prostaglandin synthesis and is overexpressed at sites of inflammation and in several epithelial cancers. Recently, a causal link for COX-2 in epithelial tumorigenesis was shown in genetically-manipulated animal models of colon and breast carcinoma. Data indicate that COX-2 is involved in the regulation of apoptosis, angiogenesis, and tumor cell invasiveness, which appear to contribute to its effects on tumorigenesis. Multiple studies have shown that nonselective COX and selective COX-2 inhibitors effectively prevent experimental colon cancer. Furthermore, sulindac and the selective COX-2 inhibitor celecoxib were shown to regress colorectal polyps in patients with familial adenomatous polyposis. Although the exact anti-tumor mechanisms of these agents await further study, data indicate that both COX-dependent and COX-independent mechanisms may be important. In this review, the association between COX-2 and colorectal tumorigenesis and potential mechanisms of this effect are discussed. Additionally, evidence supporting the role of NSAIDs and selective COX-2 inhibitors for the prevention and treatment of human colorectal cancer is reviewed.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Apoptosis
  • Colorectal Neoplasms / metabolism*
  • Cyclooxygenase 2
  • Humans
  • Isoenzymes / physiology*
  • Membrane Proteins
  • Models, Biological
  • Neoplasm Invasiveness
  • Neoplasms / metabolism
  • Prostaglandin-Endoperoxide Synthases / physiology*
  • Prostaglandins / metabolism

Substances

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