Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition.
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/cm(2). 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.
Pentland
A P
AP
Department of Dermatology, University of Rochester Medical Center, Rochester, NY 14642, USA. alice_pentland@urmc.rochester.edu
Schoggins
J W
JW
Scott
G A
GA
Khan
K N
KN
Han
R
R
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D000068579:Celecoxib; D002455:Cell Division; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D005260:Female; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000378:metabolism; D011720:Pyrazoles; D012878:Skin Neoplasms / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D013449:Sulfonamides / Q000627:therapeutic use*; D014466:Ultraviolet Rays
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib