Inhibition of mitochondria NADH–Ubiquinone oxidoreductase (complex I) sensitizes the radioresistant glioma U87MG cells to radiation

Biomedicine & Pharmacotherapy

Jia Wang¹  Yanqin Yang²  Haoyu Dong²  Lu Zhang²  Weifeng Mao²  Xingjie Gao²  Jingkai Zhang²  Caifeng Sun²  Ying Wang²  Chuanzhou Gao²  Bin Zhang²  Bin Feng³  Han Zhang⁴ 

[1] Department of Radiotherapy, the Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China;College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China;Department of Radiotherapy, the First Affiliated Hospital, Dalian Medical University, Dalian 116044, China;Eight-year Clinical Medicine Education Program, Dalian Medical University, Dalian 116044, China;

关键词: Glioma;    Mitochondria metabolism;    Complex I;    Radioresistance;    Rotenone;    Metformin;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown