目的：观察体外环境下克唑替尼对NSCLC细胞的放射增敏效果及其潜在机制。方法以H2228及H3122细胞株为实验对象，MTT法检测不同浓度克唑替尼对NSCLC细胞的抑制作用；平板克隆形成实验分别测定NSCLC细胞在克唑替尼作用下照射以及单纯照射的SF，拟合细胞生存曲线并计算放射增敏比；流式细胞仪检测各细胞株的接受不同剂量放射线后细胞凋亡率及细胞周期分布的变化；Western Blot检测各细胞株接受放射线照射后STAT3及p-STAT3蛋白表达水平变化。结果 MTT实验：抑制率与浓度变化呈正相关。IC50分别为330 nM和102 nM。克隆形成实验：附加药物照射的细胞SF低于单纯照射组。H2228/H3122细胞株组中，SER（D0）：1.064/1.004；SER（Dq）：1.079/1.047。流式细胞术：两细胞的凋亡率与照射剂量呈正比。在H2228组细胞中G0/G1期细胞阻滞现象明显，H3122细胞各周期细胞比率未见明显变化。Western Blot法：应用克唑替尼联合时STAT3的磷酸化过程受到阻滞。H2228细胞株阻滞现象更为明显。结论克唑替尼对NSCLC H2228及H3122细胞株均有放射增敏作用，对H2228细胞株的放射增敏效果更加明显。%Objective To observe the radiosensitization of crizotinib on NSCLC cells in vitro and to explore the potential mechanisms. Methods NSCLC cell lines H2228 and H3122 were used in this study. MTT was used to investigate the cytotoxicity of crizotinib and define the IC50 for H2228 and H3122 cells. Clonogenic assay was used to determine cell SF of cells received radiation alone and crizotinib administrated for 36 h before irradiation, fitting cell survival curve and calculating the ratio radiosensitization. Flow cytometry was used to detect the cell lines of different doses of radiation to accept change rate of apoptosis and cell cycle distribution. Western Blotting was used to detect STAT3 and p-STAT3 protein levels of cell lines after irradiation. Results The inhibition rate was positively related with the concentration change. The IC50 concentration of crizotinib were 330 nM and 102 nM. In the H2228/H3122 cell group, SER (D0) were: 1.064/1.004, SER (Dq) were: 1.079/1.047. H2228 cells after the application of crizotinib, G0/G1 phase cell cycle arrest phenomenon obviously. H3122 cells for application the crizotinib after each cycle the cells did not change the ratio. Conclusion The crizotinib in non-small cell lung cancer cell lines H2228 and H3122 was radiosensitizing effect, the radiosensitizing effect on the H2228 cell line was more obvious.
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