Preventative topical diclofenac treatment differentially decreases tumor burden in male and female Skh-1 mice in a model of UVB-induced cutaneous squamous cell carcinoma
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Publisher:Oxford University Press
Citation:Burns EM, KL Tober, JA Riggenbach, JS Schick, KN Lamping, DF Kusewitt, GS Young, and TM Oberyszyn. (2013) Preventative topical diclofenac treatment differentially decreases tumor burden in male and female Skh-1 mice in a model of UVB-induced cutantous squamous cell carcinoma. Carcinogenesis 34: 370-377
Series/Report no.:2013 Edward F. Hayes Graduate Research Forum. 27th
Ultraviolet B (UVB) light is the major environmental carcinogen contributing to nonmelanoma skin cancer (NMSC) development. There are over 3.5 million NMSC diagnoses in two million patients annually, with men having a three fold greater incidence of squamous cell carcinoma (SCC) compared to women. Chronic inflammation has been linked to tumorigenesis, with a key role for the cyclooxygenase-2 (COX-2) enzyme. Diclofenac, a COX-2 inhibitor and NSAID, currently is prescribed to patients as a short-term therapeutic agent to induce SCC precursor lesion regression. However, its efficacy as a preventative agent in patients without evidence of precursor lesions but with significant UVB-induced cutaneous damage has not been explored. We previously demonstrated in a murine model of UVB-induced skin carcinogenesis, that when exposed to equivalent UVB doses, male mice had lower levels of inflammation but developed increased tumor multiplicity, burden, and grade compared to female mice. Because of the discrepancy in the degree of inflammation between male and female skin, we sought to determine if topical treatment of previously damaged skin with an anti-inflammatory, COX-2 inhibitor would decrease tumor burden and if it would be equally effective in the sexes. Our results demonstrated that despite observed sex differences in the inflammatory response, prolonged topical diclofenac treatment of chronically UVB-damaged skin effectively reduced tumor multiplicity in both sexes. Unexpectedly, tumor burden was significantly decreased only in male mice. Our data suggest a new therapeutic use for currently available topical diclofenac as a preventative intervention for patients predisposed to cutaneous SCC development before lesions appear.
Professional Biological Sciences: 2nd Place (The Ohio State University Edward F. Hayes Graduate Research Forum)