Carcinogenesis, Vol. 20, No. 10, 1939-1944,
October 1999
© 1999 Oxford University Press
Molecular Epidemiology and Cancer Prevention |
Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition
Department of Dermatology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 697, Rochester, NY 14642 and
1 Searle Co., Skokie, IL, USA
UV light is a complete carcinogen, inducing both basal and squamous cell skin cancers. The work described uses the selective COX-2 inhibitor celecoxib to examine the efficacy of COX-2 inhibition in the reduction of UV light-induced skin tumor formation in hairless mice. UVA-340 sun lamps were chosen as a light source that effectively mimics the solar UVA and UVB spectrum. Hairless mice were irradiated for 5 days a week for a total dose of 2.62 J/cm2. When 90% of the animals had at least one tumor, the mice were divided into two groups so that the tumor number and multiplicity were the same (P < 0.31). Half of the mice were then fed a diet containing 1500 p.p.m. celecoxib. Tumor number, multiplicity and size were then observed for the next 10 weeks. Ninety-five percent of the tumors formed were histopathologically evaluated as squamous cell carcinoma. COX-2 expression and activity were increased in tumors. After 10 weeks, the difference in tumor number and multiplicity in the drug-treated group was 56% of UV controls (P < 0.001). The results show that the orally administered selective COX-2 inhibitor celecoxib prevents new tumor formation after the onset of photocarcinogenesis and suggest that treatment with celecoxib may be very useful in preventing UV-induced skin tumors in humans.
Abbreviations: COX, cyclooxygenase; PGE2, prostaglandin E2 .
2 To whom correspondence should be addressed. Email: alice_pentland{at}urmc.rochester.edu
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