尼妥珠单抗提高肺腺癌放射敏感性的体外实验研究

Experimental research of Nimotuzumab to enhance radiosensitizing effects in human lung cancer cells

目的探讨尼妥珠单抗对人肺癌A549细胞系的放射敏感性影响及机制。方法实验分空白对照组(C组)、照射组(R组)、加药组(D组)、照射加药组(R+D组),利用单击多靶教学模型拟合辐射剂量效应曲线,应用细胞克隆形成实验观察各组细胞存活情况,应用流式细胞仪技术分析各组细胞周期分布和细胞凋亡率。结果 R组与R+D组平均致死剂量(D0)分别为2.727Gy、2.164Gy,准阈剂量(Dq)分别为1.102Gy、0.301Gy;两组放射增敏比SERD0为1.260、SERDq为3.661,流式细胞仪结果提示R+D组G2/M期细胞比例及细胞凋亡率增加最明显(P<0.05)。结论尼妥珠单抗对A549细胞有放射增敏作用,机制与尼妥珠单抗调控肿瘤细胞周期、诱导肿瘤细胞凋亡和减少肿瘤细胞的亚致死损伤的修复有关。

Objective To explore the effect and mechanism of Nimotuzumab on the radiosensitivity of human lung adenocarcinoma cell line A549.Methods A549 cells were divided into control group(group C),radiation therapy group(group R),drug treatment group(group D),and radiation therapy plus drug treatment group(group R+D).Radiation dose-effect curve was obtained by using single-hit multi-target model.The cell survival was detected by cloning assay.The cell cycle and cell apoptosis rate were obtained by using flow cytometry.Results The D0 values were 2.727 Gy and 2.164 Gy in group R and group R+D.The Dq values were 1.102 Gy and 0.301 Gy in group R and group R+D.The SERD0 and SERDq were 1.260 and 3.661 respectively.The results of flow cytometry indicated that a higher G2/M phase arrest and apoptosis rate were observed in R+D group(P<0.05).Conclusions Nimotuzumab is a potential radiosensitizer for lung adenocarcinoma cell line A549 in vitro,probably via regulating cell-cycle distribution,inducting apoptosis,and reducing the repair of sublethal cell damage.