To evaluate the potential radiosensitizing effect of the specific COX-2 inhibitor celecoxib (Celebrex ® ) on prostate carcinoma cells in vitro.The influence of celecoxib (concentration range 5 to 75μM) on radiation-induced cellular and clonogenic survival was investigated in prostate carcinoma cell lines PC-3, DU145, LNCaP and normal prostate epithelial cells (PrEC). Western blot analysis and ELISA were used to determine the impact of radiation alone or radiation combined with celecoxib treatment on COX-2 expression and prostaglandin E2 synthesis. To evaluate induction of celecoxib-induced apoptosis cell cycle analysis has been performed.Celecoxib (5, 10 and 25μM) in combination with single-dose irradiation of 2Gy induced a significant radiosensitization in normal prostate epithelial cells which could not be observed for any of the prostate carcinoma cell lines investigated. Increased COX-2 protein expression in PC-3 cells was obvious only after IR with 15Gy, while PGE 2 production was elevated following irradiation (2–15Gy) in a dose-dependent manner. Treatment with celecoxib alone or in combination with IR led to a dose-dependent increase in COX-2 protein expression. Nevertheless pre-treatment with celecoxib caused a marked reduction of radiation-induced enzyme activity as tested at the level of PGE 2 production, both in PC-3 and DU145 cells. Following fractionated irradiation with single doses of 2Gy, elevated COX-2 protein expression as well as enhanced PGE 2 production was observed already after the second fraction in PC-3 cells. Pre-treatment with celecoxib reduced the amount of PGE 2 significantly, but not of COX-2 protein.Our data obtained for the human prostate cancer cell lines do not indicate that a marked inhibition of prostaglandin E2 synthesis by celecoxib leads to enhanced radiosensitization. Thus, in terms of radiosensitization the analysed prostate cancer cells can be classified as non-responders to celecoxib treatment.