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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。
Objective To investigate the effect of breast cancer and ovarian cancer susceptibility gene BRCA1 on the radiosensitivity of different lung cancer patients. Methods The pcDNA3-BRCA1 expression plasmid was transfected into human lung adenocarcinoma cells by lipofection method to obtain BRCA1 overexpression transfected cells. BRCA1 siRNA was transfected into seven human lung adenocarcinoma cells to obtain transfected cells with BRCA1 gene silencing The expression of BRCA1 protein was detected by Western blot. After γ-ray irradiation, the effect of BRCA1 overexpression on the radiosensitivity of the two lung cancer cells was detected by cell clone formation assay. Results The radiosensitivity of different lung cancer cells was negatively correlated with the expression level of BRCA1. Compared with control group of pcDNA3 plasmid and control group without transfection, increasing BRCA1 expression resulted in a significant decrease in the sensitivity of lung cancer cells to radiotherapy (P <0.05). The BRCA1-induced cellular radioresistance was observed in both A-549 and HTB58 lung cancer cell lines. Transfection of NIH-H2170 lung cancer cells transfected with BRCA1 siRNA resulted in a significant increase in radiosensitivity (P <0.05) in transfected cells with BRCA1 gene silencing. Conclusions This study, for the first time, found that the expression level of BRCA1 is closely related to the radiosensitivity of lung cancer cells. It was also confirmed for the first time that changing the expression level of BRCA1 could significantly affect the radiosensitivity of lung cancer cells.