Study on enhancement of radiosensitivity in pancreatic carcinoma cell line PC-3 by NS-398

OBJECTIVE: To study the radiosensitizing effect of NS-398,a selective cyclooxygenase-2 inhibitor,on pancreatic carcinoma cell line PC-3 in vitro and investigate the possible mechanisms.METHODS:Pancreatic carcinoma cell line PC-3 was cultivated in RPMI1640.Flow cytometry analysis(FCM) was used to detect the express of COX-2.MTT assay was performed to evaluate the extent of cell proliferation which was inhibited by NS-398 and its radiosensitizing effect on PC-3 cell.FCM was applied to explore the change of cell cycle distribution.RT-PCR and FCM were applied to detect apoptosis associated gene Bcl-2 and Bax expression changes after the application of NS-398 and radiation.RESULTS:FCM showed remarkably positive COX-2 expression in PC-3 cell.The MTT assay indicated that in the NS-398 combining radiation group,the survival ratio was significantly lower compared with the radiation group((78.45±3.46)% vs(57.42±2.58)%,χ2=5.52,P=0.016).The ratio of cells obviously decreased in the S stage out of the total cells in the NS-398 combining radiation group(χ2=4.91,P=0.029),but increased significantly in the G2~M stage(χ2=3.92,P=0.041),which indicated that the distribution of cell cycles could be changed by the synergistic effect of NS-398 and radiation.The RT-PCR and FCM analysis indicated that the ratio of Bcl-2/Bax decreased after the treatment with NS-398 and radiation.CONCLUSION: NS-398 could enhance the radiosensitivity of pancreatic carcinoma PC-3 cells,which suggests that the selective cyclooxygenase-2 inhibitor would be a new kind of radiosensitizer and have a good prospect for solid tumors in radiation therapy.