厄洛替尼对人肺腺癌A549细胞的放射增敏作用  

Radiosensitizing effect of erlofinib on human lung adenocarcinoma cell line A549

作　　者：刘小群[1] 乔田奎[1] 

机构地区：[1]复旦大学附属金山医院肿瘤科,上海201508

出　　处：《中华肿瘤杂志》2013年第11期819-823,共5页Chinese Journal of Oncology

基　　金：基金项目：上海市金山区科委基金（2013-248）

摘　　要：目的探讨厄洛替尼对人肺腺癌A549细胞的放射增敏作用及机制。方法采用四甲基偶氮唑蓝（MTT）法测定厄洛替尼对细胞的抑制作用，计算半数抑制浓度（IC50）。采用细胞克隆形成实验分析厄洛替尼对A549细胞的放射增敏作用。采用流式细胞仪分析厄洛替尼对细胞周期分布和凋亡的影响。结果厄洛替尼作用48h后，A549细胞生长受到抑制，且细胞抑制率随药物浓度的升高而增加，IC50为19．26μmol／L。厄洛替尼与不同剂量的X线照射A549细胞后，与单纯照射组比较，厄洛替尼照射组的细胞存活分数（SF）下降，而且随着厄洛替尼作用时间的延长和照射剂量的增加，SF明显下降。单纯照射组、厄洛替尼24h照射组和厄洛替尼48h照射组的平均致死剂量（D0）分别为3．01、2．58和2．45Gy，准域剂量（Dq）分别为2．16、1．94和1．61Gy；厄洛替尼24h照射组和厄洛替尼48h照射组的放射增敏比（SERD0）分别为1．17和1．23。流式细胞仪检测结果显示，厄洛替尼作用A549细胞24和48h后，q／M期细胞比例增加，细胞凋亡率升高，与对照组比较，差异均有统计学意义（均P〈0．05）。结论厄洛替尼对肺腺癌A549细胞有抑制作用和放射增敏作用，其放射增敏作用机制可能与抑制细胞亚致死损伤修复、阻滞细胞于G2／M期和诱导细胞凋亡有关。Objective To explore the radiosensitizing effect of erlotinib on human lung adenocarcinoma cell line A549 cells and the related mechanisms. Methods The inhibitory effect of erlotinib on A549 ceils was assessed by MTT assay, and its IC50 concentration was calculated. The radiosensitization was evaluated by the method of clone forming assay. Flow cytometry was used to analyze the effect of erlotinib on cell cycle and apoptosis. Results The growth of A549 ceils was inhibited after the cells were exposed to erlotinib for 48 hours. Moreover, the inhibitory rates increased with the increase of erlotinib concentrations, and IC50 was 19.26 μmol/L. In contrast to the irradiation alone group, the survival rates of the cells in erlotinib plus irradiation groups decreased, and erlotinib enhanced the radiosensitivity of the A549 cells. This effect was further increased as cells were exposed to erlotinib for a longer time. In the irradiation alone group and the two groups exposed to erlotinib for 24 hours and 48 hours before irradiation, Do values were 3.01 Gy, 2.58 Gy and 2.45 Gy respectively, and Dq values were 2.16 Gy, 1.94 Gy and 1.61 Gy, respectively. In the last two groups, SERD0 values were 1.17 and 1.23, respectively. The flow cytometry analysis showed that erlotinib induced G2/M phase arrest and increased the apoptosis rate in A549 cells. With the increase of exposure time, the effects were more significant. Conclusions Erlotinib inhibits the A549 cell growth and enhances the radiosensitivity of ASd9 cells in vitro. The radiosensitizing mechanisms might be related to inhibiting repair of sublethal injury and inducing G2/M phase arrest and apoptosis.

关 键 词：肺肿瘤 厄洛替尼 放射增敏 细胞周期 细胞凋亡 细胞增殖 

分 类 号：R734.2[医药卫生—肿瘤]