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
Menée sur un modèle murin de carcinome épidermoïde de la peau induit par les ultraviolets, cette étude montre qu'un traitement topique à base de diclofénac, un anti-inflammatoire non stéroïdien inhibiteur de la cyclo-oxygénase 2, peut, à différents degrés selon le sexe, réduire la charge tumorale chez la souris ne présentant pas de lésions cutanées précurseurs
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 inflammation levels between male and female skin, we set out to determine if topical treatment of previously damaged skin with an anti-inflammatory, COX-2 inhibitor agent 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.
http://carcin.oxfordjournals.org/content/early/2012/11/02/carcin.bgs349.abstract