Inhibition of cyclooxygenase-2 activity by celecoxib does not lead to radiosensitization of human prostate cancer cells in vitro.
OBJECTIVE
To evaluate the potential radiosensitizing effect of the specific COX-2 inhibitor celecoxib (Celebrex) on prostate carcinoma cells in vitro.


METHODS
The influence of celecoxib (concentration range 5 to 75 microM) 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.


RESULTS
Celecoxib (5, 10 and 25 microM) in combination with single-dose irradiation of 2 Gy 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 15 Gy, while PGE2 production was elevated following irradiation (2-15 Gy) 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 PGE2 production, both in PC-3 and DU145 cells. Following fractionated irradiation with single doses of 2 Gy, elevated COX-2 protein expression as well as enhanced PGE2 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.


CONCLUSIONS
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.
Ohneseit
Petra Anna
PA
Division of Radiobiology and Molecular Environmental Research, Department of Radiation Oncology, University of Tübingen, Germany.
Krebiehl
Guido
G
Dittmann
Klaus
K
Kehlbach
Rainer
R
Rodemann
Hans Peter
HP
D017209:Apoptosis; D000068579:Celecoxib; D002453:Cell Cycle; D045744:Cell Line, Tumor / Q000187:drug effects* / Q000528:radiation effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D011720:Pyrazoles / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D015232:Dinoprostone