Effects of Selective COX-2 Inhibitor on DNA Repairing after Irradiation

Objective 　To investigate the effect s of a selective COX-2 inhibitor-celecoxib on DNA repairing af ter X-rays irradiation, in order to elucidate the possible mechanism of the radiosensitization of selective COX-2 inhibitor. Methods 　Human cervical carcinoma cells ( HeLa) were cultured in vit ro and exposed to different doses of celecoxib for 48h then with and without radiation ( 6 Gy), flow cytomet ry sub-G1fluorescence parameter line was performed to analyze the change of the apoptosis and cell cycle dist ri-bution. The DNA damage and repair were detected by single cell gel elect rophoresis assay. Semi-quantita-tive RT2PCR and Western blot were used to measure the mRNA and protein level of ku70 and ku80 in HeLa cell lines t reated with celecoxib. Results 　Celecoxib had no effect on the cell cycle dist ribution of HeLa cell lines, but it induced apoptosis increasing dependent on celecocib doses. Radiation-induced apop-tosis was enhanced af ter Hela cells t reated with celecoxib (enhancement factor = 6. 96 at100μmol/ L), and the radiation2induced G2/ M arrest was markedly decreased by celecoxib〔Radiation group ( RT) : G2 / M 32. 35 %, 100μmol/ L celecoxib + RT : G2 / M 5. 95 %〕. The DNA damage induced by radiation was not increased, but the DNA repair was reduced in Hela cells t reated with celecoxib (60μmol/ L) for 48h, the mRNA and protein level of ku70 and ku80 were also significantly decreased ( P < 0. 05) . Conclusion 　The result s suggest that the possible mechanism of radiosensitization of a selective COX-2 inhibitor was relat-ed to inhibition of DNA repair including reduced G2/ M arrest cells and decreased DNA-PK expression.