Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors.

Abstract

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.

• Authors: J L Masferrer, K M Leahy, A T Koki, B S Zweifel, S L Settle, B M Woerner, D A Edwards, A G Flickinger, R J Moore, K Seibert
• Journal: Cancer research (Cancer Res) Vol. 60 Issue 5 Pg. 1306-11 (Mar 01 2000) ISSN: 0008-5472 [Print] United States
• PMID: 10728691 (Publication Type: Journal Article)

Chemical References

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

Topics

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