College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China; Department of Radiotherapy, the Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China.
Biomed Pharmacother. 2020 Sep;129:110460. doi: 10.1016/j.biopha.2020.110460. Epub 2020 Jul 1.
Radiation is a current standard treatment of glioma. The fractionated radiotherapy with low dose of radiation over weeks has been employed in glioma patients, while radiotherapy can only offer palliation due to the radioresistance. We cumulatively radiated a glioblastoma cell line, U87MG, and screened radioresistant glioma cells. A transcriptome sequencing was performed to analyze the transcription differences between the raidoresistant and control cells, which showed the mitochondria NADH-ubiquinone oxidoreductase (Complex I) subunits were up-regulated in the radioresistant cells. The copy numbers of mitochondria were increased in the radioresistant glioma cells. After using mitochondria Complex I inhibitors, rotenone and metformin, to treat glioma cells, we found the resistant glioma cells re-sensitized to radiation. These results demonstrate that Complex I is associated with the fractioned radiation-induced radioresistance of glioma and would be a potent target for clinical radiotherapy of glioma.
辐射是胶质母细胞瘤的一种标准治疗方法。在胶质母细胞瘤患者中，采用低剂量分次放射治疗数周，但由于肿瘤的放射抗性，放疗只能提供姑息治疗。我们对胶质母细胞瘤细胞系 U87MG 进行累积辐射，并筛选出放射抗性的胶质瘤细胞。进行转录组测序以分析耐辐射和对照细胞之间的转录差异，结果显示耐辐射细胞中线粒体烟酰胺腺嘌呤二核苷酸-泛醌氧化还原酶（复合物 I）亚基上调。耐辐射胶质瘤细胞中线粒体的数量增加。在用线粒体复合物 I 抑制剂鱼藤酮和二甲双胍处理胶质瘤细胞后，我们发现耐药的胶质瘤细胞对辐射重新敏感。这些结果表明，复合物 I 与分次辐射诱导的胶质瘤放射抗性有关，可能成为胶质细胞瘤临床放疗的有效靶点。
