非小细胞肺癌EGFR基因突变与放射敏感性的相关性

发布时间：2018-10-29 12:21

【摘要】：目的探讨表皮生长因子受体(EGFR)基因突变与非小细胞肺癌(NSCLC)放射敏感性的相关性及可能机制。方法选取EGFR基因突变的NSCLC细胞株PC-9、H1975和EGFR野生型NSCLC细胞株A549。克隆成型实验检测放射敏感性,流式细胞术检测细胞凋亡和细胞周期,Western blot检测凋亡蛋白和修复蛋白表达。结果 PC-9、H1975细胞放射敏感性明显高于A549细胞,4 Gy照射下克隆存活率分别为10.0%、5.5%和44.3%;4 Gy照射后48 h PC-9和H1975细胞凋亡率显著高于A549细胞,分别为18.300%、17.533%和11.733%。A549细胞发生G_0/G_1期阻滞显著高于PC-9、H1975细胞,4 Gy照射后48 h G_0/G_1期细胞分别为74.480%、70.293%和57.016%。A549细胞在4 Gy照射后促凋亡蛋白Bax表达缺失,凋亡蛋白Caspase-3、抗凋亡蛋白Bcl-2、修复蛋白DNA-PKcs在24 h仍有表达。而PC-9、H1975细胞在4 Gy照射后Bax、Caspase-3表达增多,Bcl-2不表达,DNA-PKcs表达减少。结论 EGFR 19外显子缺失突变细胞PC-9和21外显子点突变细胞H1975,相对EGFR野生型细胞A549对放射线敏感,其机制与细胞周期G_0/G_1期阻滞、Bax表达增多、DNAPKcs、Bcl-2表达降低有关。
[Abstract]:Objective to investigate the relationship between epidermal growth factor receptor (EGFR) gene mutation and (NSCLC) radiosensitivity in non-small cell lung cancer (NSCLC). Methods NSCLC cell line PC-9,H1975 and EGFR wild type NSCLC cell line A549 with EGFR gene mutation were selected. The radiosensitivity was detected by clone forming assay, apoptosis was detected by flow cytometry and apoptotic protein and repair protein were detected by cell cycle, Western blot. Results the radiosensitivity of PC-9,H1975 cells was significantly higher than that of A549 cells. The clone survival rate of 4 Gy irradiated cells was 5.0% and 44.3%, respectively. 4 the apoptotic rate of PC-9 and H1975 cells 48 h after Gy irradiation was significantly higher than that of A549 cells, which was 18.300% and 17.533%, respectively, and the G_0/G_1 phase arrest of 11.733%.A549 cells was significantly higher than that of PC-9,H1975 cells. 4 at 48 h after Gy irradiation, 74.480% of the cells in the G_0/G_1 phase and 70.293% of the 57.016%.A549 cells were exposed to 4 Gy irradiation. The expression of apoptotic protein Bax was absent, and the apoptotic protein Caspase-3, anti-apoptotic protein Bcl-2, was found. The repair protein DNA-PKcs was still expressed at 24 h. However, the expression of Bax,Caspase-3 in PC-9,H1975 cells increased after 4 Gy irradiation, Bcl-2 was not expressed and DNA-PKcs expression was decreased. Conclusion EGFR 19 exon deletion mutant cell line PC-9 and exon 21 point mutant cell line H1975are more sensitive to radiation than EGFR wild type cell A549, and its mechanism is related to cell cycle G_0/G_1 phase arrest, Bax expression and DNAPKcs,. The decrease of Bcl-2 expression is related to.
【作者单位】：广东药科大学;广州军区广州总医院肿瘤科;
【基金】：国家自然科学基金面上项目(编号:81472172)
【分类号】：R734.2

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