Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors

Jaime L. Masferrer, Kathleen M. Leahy, Alane T. Koki, Ben S. Zweifel, Steven L. Settle, B. Mark Woerner, Dorothy A. Edwards, Amy G. Flickinger, Rosalyn J. Moore, Karen Seibert

Research output: Contribution to journalArticlepeer-review

1283 Scopus citations


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.

Original languageEnglish
Pages (from-to)1306-1311
Number of pages6
JournalCancer research
Issue number5
StatePublished - Mar 1 2000


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