不同非小细胞肺癌细胞株中DNA-PKcs的表达及其与放射敏感性的关系  

Correlation of DNA-dependent protein kinase catalytic subunit expression to radiosensitivity of non-small cell lung cancer cell lines

作　　者：潘燚[1] 李伟雄[1] 李俊铭[1] 朱建权[2] 梁亦强[1] 郭爱林[2] 

机构地区：[1]广东省人民医院肿瘤中心放疗科,广东广州510080 [2]广东省人民医院医学研究中心,广东广州510080

出　　处：《癌症》2009年第7期714-717,共4页Chinese Journal of Cancer

基　　金：广东省医学科学技术研究基金(No.A2006014);广东省自然科学基金(No.06020905)~~

摘　　要：背景与目的:DNA依赖蛋白激酶催化亚基(DNA-dependent protein kinase catalytic subunit,DNA-PKcs)在电离辐射引起的DNA双链断裂的修复过程中起着关键作用,可影响组织细胞对放射治疗的敏感性。本研究通过检测DNA-PKcs在不同组织学类型非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞中的表达情况,探讨其与放射敏感性的关系。方法:Westernblot及DNA-PK活性分析法检测NSCLC细胞株A549、H1299、L78、PGCL3和H460中DNA-PKcs的含量与活性。成克隆实验分别测定各细胞株照射后的剂量-存活曲线,并分析放射敏感性与DNA-PKcs的关系。结果:成克隆实验结果显示:不同NSCLC细胞株的放射敏感性不同,A549细胞2Gy剂量照射下的存活分数(survival fractionat2Gy,SF2)为0.74,H1299细胞为0.25,H460细胞为0.21,PGCL3细胞为0.48,L78细胞为0.58。Westernblot显示各NSCLC细胞株中DNA-PKcs的表达有差异,A549细胞的DNA-PKcs表达水平为3.26±0.98,L78细胞为0.51±0.07,H1299细胞为0.51±0.11,H460细胞为0.86±0.23,PGCL3细胞为2.60±0.76。A549细胞的DNA-PKcs活性为8.30±1.03,H1299细胞为2.45±0.52,H460细胞为0.11±0.02,PGCL3细胞为4.13±0.87,L78细胞为0.42±0.07。在腺癌及大细胞癌中SF2与DNA-PKcs含量(P<0.05,r=0.95)及活性(P=0.03,r=0.98)呈线性相关。结论:在腺癌及大细胞癌中,DNA-PKcs是判断细胞放射敏感性的重要因素。Background and Objective： DNA-dependent protein kinase catalytic subunit （DNA-PKcs） plays an important role in repairing irradiationinduced DNA double-strand break （DSB）, and affects the radiosensitivity of tissue cells. This study was to detect the expression of DNA-PKcs in different non-small cell lung cancer （NSCLC） cell lines and evaluate its correlation to radiosensitivity. Methods： The content and activity of DNA-PKcs in five NSCLC cell lines A549, H1299, L78, PGCL3 and H460 were measured by Western blot and the DNA-PK activity assay. Cell survival was analyzed using clonogenic formation assay. Results： The radiosensitivities of five NSCLC cell lines were different. The values of survival fraction at 2 Gy （SF2） were 0.74 in A549 cells, 0.25 in H1299 cells, 0.21 in H460 cells, 0.48 in PGCL3 cells, and 0.58 in L78 cells. The protein levels of DNA-PKcs were 3.26±0,98 in A549 cells, 0.51±0.07 in L78 cells, 0.51±0,11 in H1299 cells, 0.86±0.23 in H460 cells, and 2.60±0.76 in PGCL3 cells. The activity values of DNA-PKcs were 8,30±1.03 in A549 cells, 2.45±0.52 in H1299 cells, 0.11±0.02 in H460 cells, 4.13±0.87 in PGCL3 cells, and 0.42±0.07 in L78 ceils. In adenocarcinoma and large cell carcinoma cell lines, SF2 were correlated to DNA-PKcs content （P〈0.05, r=0.95） and activity （P=0.03, r= 0.98）. Conclusion： DNA-PKcs is an important factor to predict the radiosensitivity in adenocarcinoma and large cell lung cancer cell lines.

关 键 词：DNA—PKcs 肺肿瘤 非小细胞肺癌细胞株 放射 敏感性 

分 类 号：R734.2[医药卫生—肿瘤]