Treatment with 5-fluorouracil and celecoxib displays synergistic regression of ultraviolet light B-induced skin tumors.
Standard chemotherapeutic agents used for the treatment of pre-cancerous skin lesions and non-melanoma skin cancers are not completely effective. Several studies have suggested that repeated inflammatory sunburn reactions, which include the induction of cyclooxygenase-2 (COX-2) and the subsequent production of prostaglandins, play a role in skin cancer development. COX-2 inhibition has been demonstrated to be a potent means of preventing skin cancer development in mice; however, COX-2 inhibitors alone are not effective as chemotherapeutic agents. Data in a variety of cancer types suggest greater efficacy in treating tumors with combination chemotherapies. Therefore, we hypothesized that a combination of the chemotherapeutic agent 5-fluorouracil (5-FU) and the COX-2 inhibitor and anti-inflammatory drug celecoxib would act synergistically to regress tumors in a murine model of ultraviolet light B- (UVB-) induced carcinogenesis. We found that topical treatment with 5-FU and celecoxib together was up to 70% more effective in reducing the number of UVB-induced skin tumors than 5-FU treatment alone. Our data suggest that more effective chemotherapy regimens can be developed to treat the millions of pre-cancerous and cancerous skin lesions that arise every year, which could ultimately lead to a significant reduction in costs and cosmetic defects (scarring) associated with surgical interventions.
Wilgus
Traci A
TA
The Ohio State University, Department of Pathology, Columbus, Ohio, USA.
Breza
Thomas S
TS
Tober
Kathleen L
KL
Oberyszyn
Tatiana M
TM
D000287:Administration, Topical; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000068579:Celecoxib; D002455:Cell Division / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D051379:Mice; D008812:Mice, Hairless; D011720:Pyrazoles; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects
D000964:Antimetabolites, Antineoplastic; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D015232:Dinoprostone; D005472:Fluorouracil