Celecoxib, a Cyclooxygenase 2 Inhibitor as a Potential Chemopreventive to UV-Induced Skin Cancer

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Abstract
Objective To assess the preventive effect of a cyclooxygenase 2 inhibitor, celecoxib (Celebrex; G.D. Searle & Co, Skokie, Ill), in UV-induced skin cancer in hairless mice. Design Randomized dose-response study. A total of 75 SKH-HR-1 female hairless mice, aged 2 months, were randomized into control, low-dose (200 mg twice daily human dose equivalent), and high-dose (400 mg twice daily human dose equivalent) celecoxib treatment groups. Animals received 1 J/cm2 daily (5 d/wk) total irradiation. The animals were evaluated weekly for appearance of tumors, and the data were analyzed with respect to tumor latency period and tumor multiplicity using statistical software and Wilcoxon rank sum analyses, respectively. Prostaglandin E2 levels in the blood and skin were assessed in each group. Setting Veterans Affairs Medical Center, Research and Dermatology Services. Intervention Animals received restricted diets containing the Food and Drug Administration–approved human equivalent doses of 200 mg (low dose) and 400 mg (high dose) of celecoxib twice daily. Controls received no drug. Tumors were induced in all animals with an equivalent UV dose. Main Outcome Measures Animals were evaluated weekly for the appearance of tumors, and data were analyzed with regard to tumor latency period and tumor multiplicity. Constitutive prostaglandin E2 levels in blood and epidermis were assessed in each group. Results Low doses and high doses of celecoxib significantly lengthened the tumor latency period (P<.03 and P<.003, respectively) and reduced tumor multiplicity (P<.005 and P<.001, respectively) compared with controls. There were no differences in the constitutive levels of blood or epidermal prostaglandin E2 in the low- or high-dose treated animals compared with controls when analyzed at study termination. Conclusions Celecoxib is an effective and safe chemopreventive agent in UV carcinogenesis. The epidemiologic, laboratory, and animal studies of the influence of celecoxib on cancer incidence and its low association with systemic adverse effects have led to a potentially new therapeutic approach for the prevention of skin cancer.