吉非替尼对肺癌细胞株H358放疗敏感性的影响及其机制

背景与目的表皮生长因子受体(epidermal growth factor receptor,EGFR)是决定放疗效应的重要因素,它的过表达或激活常与包括非小细胞肺癌在内的肿瘤放疗抵抗相关,因而阻断EGFR的信号通路是增强放疗敏感性很有潜力的治疗策略。本研究旨在观察小分子EGFR酪氨酸激酶抑制剂吉非替尼与放疗联合是否有提高非小细胞肺癌细胞株H358放疗敏感性的作用以及探索其分子机制。方法将非小细胞肺癌细胞株H358分为X线组和X线+吉非替尼组,前者采用单纯X线照射,后者经1mol/L吉非替尼作用24h后再行X线照射。克隆形成实验比较两组细胞放射敏感性,免疫荧光激光共聚焦显微镜观察X线照射后各时间点细胞核中磷酸化γ-H2AX及EGFR焦点在细胞中的定位情况,Westernblot法检测放疗后核蛋白中EGFR的表达。结果克隆形成实验中X线+吉非替尼组各个剂量点的细胞存活率均少于X线组,可见X线+吉非替尼组对放疗更敏感。免疫荧光激光共聚焦显示,X线+吉非替尼组比X线组各时段细胞核内γ-H2AX焦点数增加,持续的时间也更长。EGFR免疫荧光及Westernblot结果显示,X线组EGFR在放疗后1h内入核,而X线+吉非替尼组EGFR不在核内表达,仍位于细胞浆内。对Westernblot结果用SPSS13.0进行统计学分析,其差异有统计学意义(P=0.042)。结论吉非替尼可能是通过抑制EGFR放疗后入核进行损伤后DNA双链断裂修复,而起到对NSCLC细胞株H358放疗增敏的作用。

Effection and Mechanism of Radiosensitivity of Non-small Cell Lung Cancer Cel Line H358 Following Gefitinib Treatment

Background and objective e epidermal growth factor receptor (EGFR) is an important determinant of radioresponse, the elevated expression and activity of which frequently correlates with radioresistance in several cancers, including non-small-cell lung carcinoma (NSCLC). the molecular blockade of EGFR signaling is a promising therapeutic strategy for the enhancement of the cytotoxic the ects of radiotherapy. the aims of the present study are to observe whether ge tinib, a selective EGFR tyrosine kinase inhib...