塞来昔布对人肝癌细胞株HepG2的放射增敏作用研究

目的探讨COX-2抑制剂塞来昔布对体外培养的HepG2细胞放射增敏作用及其可能的机制,为提高肝癌的放疗效果提供实验依据。方法集落形成法绘制细胞存活曲线,计算增敏比;流式胞仪检测塞来昔布对细胞周期及凋亡的影响;免疫细胞化学染色法检测塞来昔布作用后HepG2细胞的Bcl-2、Casepase-3的表达情况。结果集落形成实验计算得单纯照射组D0=2.57Gy、Dq=2.62Gy,药物＋照射组D0=2.18Gy、Dq=1.89Gy,增敏比SER=1.18。塞来昔布作用48h后,流式细胞仪检测发现细胞周期时相分布发生明显变化,G0/G1期细胞比例增加,S期细胞减少,细胞凋亡率增加。免疫细胞化学染色法观察塞来昔布对凋亡蛋白Bcl-2、Caspase-3表达的影响,发现塞来昔布作用48h后Bcl-2的表达无明显变化,Caspase-3的表达增强。结论塞来昔布具有较强的放射增敏作用,作用机制可能与塞来昔布影响细胞周期的分布,促进细胞凋亡,抑制细胞亚致死性损伤修复有关。

Radiosensitivity Enhancement By Celecoxib On Human Hepatocellular Carcinoma Cell Line HepG2

Objective To approach the radiation-enhancing effects and underlying mechanisms of celecoxib on the cell line HepG2 of hepatocellular carcinoma,and try to provide experimental basis for enhancing the therapeutic effect of hepatocellular carcinoma.Methods The radio sensitization of celecoxib was measured by clongenic assay,and the survival curve was described.Cell cycle changes and apoptosis were detected via flow cytometry（FCM）.The Bcl-2 and Caspase-3 expression were detected by inmmunocytochemical method.Results The value of D0,Dq,SF2 and N in the group of irradiation alone were 2.57Gy,2.62Gy,the value of D0,Dq 2.18Gy,1.89Gy.The radiation enhancement ratio（SER） was 1.18 treated by celecoxib for 48h.It was shown that celecoxib induce HepG2 cells arrest in G0/G1 phase.After exposure to celecoxib for 48h,the expression of Caspase-3 was up-regulation when the expression of Bcl-2 had no changes.Conclusions Celecoxib has the effect of enhancing radiosensitivity in HepG2 cell lines.The mechanism of it may be involving repair inhibition of sublethal damage,redistribution of cell cycle and regulation of the expression of apoptosis related gene by celecoxib.