Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors

Cancer Res. 2000 Mar 1;60(5):1306-11.


We provide evidence that cyclooxygenase (COX)-2-derived prostaglandins contribute to tumor growth by inducing newly formed blood vessels (neoangiogenesis) that sustain tumor cell viability and growth. COX-2 is expressed within human tumor neovasculature as well as in neoplastic cells present in human colon, breast, prostate, and lung cancer biopsy tissue. COX-1 is broadly distributed in normal, as well as in neoplastic, tissues. The contribution of COX-2 to human tumor growth was indicated by the ability of celecoxib, an agent that inhibits the COX-2 enzyme, to suppress growth of lung and colon tumors implanted into recipient mice. Mechanistically, celecoxib demonstrated a potent antiangiogenic activity. In a rat model of angiogenesis, we observe that corneal blood vessel formation is suppressed by celecoxib, but not by a COX-1 inhibitor. These and other data indicate that COX-2 and COX-2-derived prostaglandins may play a major role in development of cancer through numerous biochemical mechanisms, including stimulation of tumor cell growth and neovascularization. The ability of celecoxib to block angiogenesis and suppress tumor growth suggests a novel application of this anti-inflammatory drug in the treatment of human cancer.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Anticarcinogenic Agents / therapeutic use*
  • Celecoxib
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • Cyclooxygenase Inhibitors / therapeutic use*
  • Humans
  • Immunohistochemistry
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / biosynthesis
  • Isoenzymes / pharmacology*
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / blood supply
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms, Experimental / blood supply
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / metabolism
  • Neovascularization, Pathologic / drug therapy*
  • Prostaglandin-Endoperoxide Synthases / biosynthesis
  • Prostaglandin-Endoperoxide Synthases / pharmacology*
  • Pyrazoles
  • Rats
  • Sulfonamides / pharmacology*
  • Sulfonamides / therapeutic use*


  • Anticarcinogenic Agents
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Pyrazoles
  • Sulfonamides
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Celecoxib