EGFR酪氨酸激酶区域突变对NSCLC放疗敏感性影响的初步研究  

Effect of the mutations in the tyrosine kinase domain of EGFRon the radiation sensitivity in NSCLC

作　　者：王振[1,2] 武新虎[1,2] 李静[1,2] 刘志冰[1,2] 沈泽天[1,2] 姜万荣[1,2] 朱锡旭[1,2] 

机构地区：[1]南京大学医学院临床学院 [2]南京军区南京总医院放疗科,江苏南京210002

出　　处：《中华肿瘤防治杂志》2013年第10期741-743,共3页Chinese Journal of Cancer Prevention and Treatment

基　　金：南京军区医药卫生科研项目(10MA098)

摘　　要：目的:探讨非小细胞肺癌(NSCLC)组织中表皮生长因子受体(EGFR)酪氨酸激酶区域突变能否影响放射治疗疗效。方法:选取野生型EGFR和突变型EGFR细胞株A549和H1975,分别进行不同剂量的X射线照射后,用克隆细胞计数的方法计算细胞生存分数(SF),并采用SPSS 13.0软件按线性二次模型拟合细胞存活曲线,计算α/β值。免疫荧光技术观察磷酸化H2AX(γH2AX)焦点数的变化,推测DNA双链断裂后修复动力学。结果:H1975及A549细胞SF2值分别为0.62和0.89,α/β分别为4.00和0.19。H1975细胞SF2较A549小,差异有统计学意义,P<0.05;但α/β值较大,差异有统计学意义,P<0.05。2种细胞株在照射4Gy后15min开始出现γH2AX焦点数增多,但是H1975细胞株较A549多,于3h时保持约70%,24h时仍有约25%,而A549细胞株在照射后3h消失接近90%。结论:NSCLCEGFR酪氨酸激酶区域突变能增加放射敏感性,可成为预测放射治疗疗效的一个指标。OBJECTIVE： To explore the effects of the mutations in the tyrosine kinase domain （TKD） of EGFR on radiation treatment in NSCLC. METHODS： A549 and H1975 were irradiated at various doses. By using clonogenic sur- vival, the radiosensitivity was investigated. The SPSS 13.0 software was applied for fitting the cell survival curve by line- ar-quadratic model. Surviving fraction （SF） values and α/β values were plotted as a function of radiation dose. Using 7H2AX foci as a surrogate for double-strand DNA break （DSB）,the rates of DSB repair between A549 and H1975 were compared. RESULTS： The SF2 values of H1975 and A549 were 0.62 and 0. 89 , respectively. The α/βvalues of H1975 and A549 were 4.00 and 0.19 , respectively （P%0.05）. The clonogenic survival of H1975 in response to IR was reduced compared with A549,and α/β values of H1975 was higher than that of A549. H1975 showed a significantly lower rate of DSB resolution compared with A549 and retain nearly 70% of yH2AX foci at 3 hours and 25 % foci at 24 hours following IR and 90M at 3 hours. H1975 exhibit delayed kinetics of DNA repair. CONCLUSIONS： NSCLC with kinase domain mu- tations in the epidermal growth factor receptor are sensitive to ionizing radiation. It may provide new insight into effective treatment of NSCLC with radiotherapy.

关 键 词：EGFR突变 非小细胞肺癌 放射敏感性 DNA修复 

分 类 号：R734.2[医药卫生—肿瘤]