Treatment of actinic keratosis through inhibition of cyclooxygenase-2: Potential mechanism of action of diclofenac sodium 3% in hyaluronic acid 2.5%

Abstract

Cyclooxygenase-2 (COX-2) and its metabolic product prostaglandin E2 (PGE2) are induced in response to growth factors, inflammatory cytokines, tumor promoters, activated oncogenes, and, in the skin, ultraviolet (UV) radiation. Accumulating evidence suggests a role for the COX-2/PGE2 pathway in tumorigenesis in various tissue types including cutaneous squamous cell carcinoma. There is also strong evidence for a role in the development of actinic keratoses (AKs) — common dysplastic lesions of the skin associated with UV radiation overexposure — considered as part of a continuum with skin cancer. Non-steroidal anti-inflammatory drugs (NSAIDs) exert their anti-inflammatory, analgesic, and antipyretic effects by reversibly or irreversibly acetylating COX isoforms, inhibiting downstream prostaglandins, and may have a chemopreventive role in malignancies, including skin cancer. Topical treatment of AK lesions with the NSAID diclofenac sodium 3% in combination with hyaluronic acid 2.5% has been shown to be effective and well tolerated, although the mechanism of action remains to be elucidated.