塞来昔布对人鼻咽癌 CNE －2细胞放疗的增敏作用

摘要

目的：探讨塞来昔布对人鼻咽癌 CNE －2细胞的放射增敏作用及其可能机制。方法：四唑盐比色法（MTT）测定塞来昔布对人鼻咽癌 CNE －2细胞株的抑制率。采用克隆形成实验检测塞来昔布处理的 CNE －2细胞经不同剂量 X 线（0、2、4、6、8和10Gy）照射后的存活分数（SF），并通过单击多靶模型拟合细胞存活曲线，计算增敏比（SER）。流式细胞仪（FCM）分析细胞周期分布及凋亡率。结果：MTT 实验显示塞来昔布在（10～80）μg／ml 范围内对 CNE －2细胞有抑制作用，抑制率与浓度、时间呈依赖关系；在2～10Gy 照射范围内，10、20、40、80μg／ml 塞来昔布处理后的 SF 均低于0μg／ml（P ＜0．05），且 SF 随塞来昔布浓度的增加而降低；相对于0μg／ml，10、20、40、80μg／ml 塞来昔布处理后的 SER 分别为1．06、1．79、2．29和3．34；流式细胞仪测得塞来昔布可呈浓度依赖的方式诱导 CNE －2细胞凋亡（P ＜0．05），S 期细胞比例降低，G2／M期细胞比例升高。结论：塞来昔布能抑制人鼻咽癌 CNE －2细胞增殖，诱导 CNE －2细胞细胞周期阻滞，促进细胞凋亡，具有放疗增敏作用。%Objective:To investigate radiotherapy sensitization effect of celecoxib on nasopharyngeal carcinoma cell line CNE -2 and its possible mechanism.Methods:MTT was applied to detect the inhibition rate of celecoxib on nasopharyngeal carcinoma cell line CNE -2.The clone formation assay was applied to investigate the survival fraction (SF)of the CNE -2 cells treated with celecoxib after different doses of X -ray(0,2,4,6,8 and 10Gy)irradiation. The sensitization enhancement ratio(SER)was calculated by cell survival curve fitted with the target model .The cell cycle distribution and apoptosis rate were detected by flowcytometry.Results:Celecoxib inhibited the growth of CNE -2 cells and it was in a dose and time -dependent manner in range of (10 ~80)μg/ml.In 2 ~10Gy irradiation range, the SF of 10,20,40,80μg/ml celecoxib were lower than that of 0μg/ml(P <0.05),and SF declined with the in-crease of concentration of celecoxib.Compared with 0μg/ml celecoxib,SER of 10,20,40,80μg/ml celecoxib after treatment were 1.06,1.79,2.29 and 3.34,respectively.Celecoxib induced the apoptosis of CNE -2 cells in a dose -dependent manner(P <0.05).Moreover,celecoxib reduced the proportion of S phase and increased the proportion of G2 /M phase.Conclusion:Celecoxib can inhibit the proliferation of nasopharyngeal carcinoma cell line CNE -2 and has the effect of radiation sensitization through cell cycle blocking and acceleration of apoptosis.