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Celecoxib, a Cyclooxygenase 2 Inhibitor as a Potential Chemopreventive to UV-Induced Skin Cancer
A Study in the Hairless Mouse Model
Ida F. Orengo, MD;
Janette Gerguis, BSc;
Rhea Phillips, MD;
Adrian Guevara, BSc;
Alan T. Lewis, MD;
Homer S. Black, PhD
Arch Dermatol. 2002;138:751-755.
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.
From the Department of Dermatology, Baylor College of Medicine (Drs
Orengo, Phillips, Lewis, and Black, Ms Gerguis, and Mr Guevara), and the Photobiology
Laboratory, Veterans Affairs Medical Center (Drs Orengo and Black, and Ms
Gerguis), Houston, Tex.
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