西妥昔单抗对肺腺癌A549细胞株辐射增敏作用的研究  

Radiosensitization of Cetuximab on pulmonary adenocarcinoma A549 cells line

作　　者：姚志峰[1,2] 姚建新[2] 徐国平 刘永彪 

机构地区：[1]南京医科大学第一附属医院肿瘤放射治疗科南京,210029 [2]江苏联合职业技术学院南京卫生分院医学影像系

出　　处：《实用肿瘤学杂志》2013年第1期11-16,共6页Practical Oncology Journal

基　　金：江苏高校优势学科建设工程资助项目（JX10231801）;江苏省医学创新团队与领军人才资助项目（LJ201123）

摘　　要：目的探讨西妥昔单抗（Cetuximab，C225）对人肺腺癌A549细胞株的辐射增敏作用及其机制。方法体外培养人肺腺癌A549细胞株，经不同浓度的C225作用后，使用CCK-8法测定细胞增殖抑制率，计算mC225的半数抑制浓度（Ic50），并将Ic50的1／5作为后续实验的浓度。采用克隆形成方法观察C225对细胞辐射敏感性的影响，按多靶单击模型拟合细胞存活曲线，计算辐射增敏比（SER）。流式细胞仪检测细胞凋亡以及细胞周期情况。结果C225均抑制了细胞的增殖，并呈现明显的量-效关系，其IC50为18．24μg／mL。与单独照射组相比，加药照射组的sF2、D3D4均下降（P〈0．05），SERoo为1．40。C225联合x线照射明显增强了辐射诱导的细胞凋亡（P〈0．05）。C225使细胞阻滞于G0／G1期（P〈0．05），单独照射组G：／M期细胞比例增加（P〈0．05），C225＋照射组同时出现G0／G1、G2／M期细胞阻滞（P〈0．05）；与对照组相比，C225组、单独照射组以及C225＋照射组s期细胞比例均下降（P〈0．05）。结论C225对A549细胞株具有辐射增敏作用，其机制可能与C225抑制细胞的生长增殖和受照射后亚致死性损伤的修复，增加细胞凋亡以及诱导细胞G0／G1期阻滞有关。Objective To explore whether Cetuximab （C225）can enhance the radiosensitization to hu- man pulmonary adenocarcinoma A549 cells line in vitro or to initially disclosure its mechanism. Methods A549 cells were cultured in vitro and treated with different concentrations of C225. Cell Counting Kit - 8 （ CCK8 ） assay was utilized to measure the inhibition of cell proliferation and determine 50% inhibition concentration （ IC50） , and then 1/5 IC50 was selected as the concentration in the follow - up experiments. The radiosensitizing effect of C225 on A549 cells was investigated by clonogenic assay. The cell survival curve was fitted by single - hit multi - target model and sensitizing enhance rate （SER）was calculated. Apoptosis and cell cycle distribution of A549 cells were measured by flow - cytometry （ FCM ） analysis. Results The proliferation of A549 cells was inhibited which showed an obvious dose - effect relationship,and the ICs0 of 48 h was 18.24 p.g/mL. The group of C225 plus radiation displayed the values of SF2, Do, Dq, which were significantly lower than those of radiation alone group（P 〈 0.05 ） ,and the sensitizing enhance rate（SER） of DO was 1.40. C225 plus radiation significantly enhanced the radiation - induced apoptosis in A549 cells（P 〈 0.05）. The cell cycle analysis showed that cells arrested in Go/Gj phase by C225 treatment （P 〈 0.05 ）. The number of cells in G2/M phase was increased in radiation group （ P 〈 0.05） ,and cells in C225 plus radiation group were arrested both in G0/G1 and G2/M phrases（P 〈0.05）. The number of cells in S phrase of three groups was decreased,compared with control group（ P 〈 0.05 ）. Conclusion C225 could enhance the radiosensitivity of A549 cells line,which is probably associated with the inhibition of proliferation and sub - lethal damage repair of tumor cells. The enhancement of radiation - induced apoptosis andcell cycle was arrested in Go/G1 phase.

关 键 词：西妥昔单抗 肺腺癌A549细胞株 细胞周期 凋亡 辐射敏感性 

分 类 号：R734.2[医药卫生—肿瘤]