中文摘要：

目的探讨乳腺癌和卵巢癌易感基因BRCA1对不同肺癌放射治疗敏感性的影响。方法采用脂质转染方法将pcDNA3-BRCA1表达质粒转染到人肺腺癌细胞获得BRCA1高表达转染细胞,将BRCA1 siRNA转染到7种人肺腺癌细胞获得BRCA1基因沉默的转染细胞;采用Western blot方法检测BRCA1蛋白表达水平的变化;γ射线照射后,采用细胞克隆形成方法检测BRCA1高表达对两种肺癌细胞放射敏感性的影响。结果不同肺癌细胞的放射治疗敏感性与其所含的BRCA1表达水平成负相关。与＂空＂pcDNA3质粒细胞和无转染母细胞的对照组相比,提高BRCA1表达水平可导致肺癌细胞对放射治疗的敏感性明显下降（P〈0.05）。BRCA1诱导的细胞耐辐射现象可以在A-549和HTB58两种肺癌细胞系观察到。而转染BRCA1 siRNA的NIH-H2170肺癌细胞导致BRCA1基因沉默的转染细胞则放射治疗敏感性明显增加（P〈0.05）。结论该研究首次发现,BRCA1表达水平与肺癌细胞的放射敏感性有着密切的关系,并首次证实改变BRCA1的表达水平可以明显影响肺癌细胞的放射治疗敏感性。

英文摘要：

Objective To investigate the effects BRCA1 on sensitivity of lung cancer cells to γ-irradiation.Methods A mammalian expression pcDNA3 vectors encoding a full-length of BRCA1 cDNA and BRCA1 siRNA were transfected into lung cancer cells.Western blot,MTT and clonogenic assays were used to determine BRCA1 protein expression and cell survival following γ-irradiation respectively.Results There is a close relationship between BRCA1 level and radiosenstivity in different lung cancer cell lines.Compared with the control cells transfected with the ＂empty＂ pcDNA3 vector and parental cells,the more survival of cells transfected with BRCA1 was observed after irradiation.The BRCA1-cuased radioresistance were observed in both A549 and HTB-58 lung cancer cell lines.However,NIH-H2170 cells transfected with BRCA1 siRNA became more sensitive to γ-irradiation.Conclusion This study,for the first time,demonstrates that the alteration of BRCA1 expression significantly affects radiosensitivity of lung cancer,indicating that BRCA1 may be an important mediator in radiotherapy of lung cancer cells.