Genistein sensitizes glioblastoma cells to carbon ions via inhibiting DNA-PKcs phosphorylation and subsequently repressing NHEJ and delaying HR repair pathways

doi:10.1016/j.radonc.2018.04.005

CORC > 近代物理研究所 > 中国科学院近代物理研究所 > 兰州重离子研究装置

	Genistein sensitizes glioblastoma cells to carbon ions via inhibiting DNA-PKcs phosphorylation and subsequently repressing NHEJ and delaying HR repair pathways
	Liu, Xiongxiong; Li, Qiang; Zhao, Ting; Ye, Fei; Zhang, Pengcheng; Jin, Xiaodong; Chen, Weiqiang; Liu, Xinguo; Niu, Yuzhen; Hirayama, Ryoichi
刊名	RADIOTHERAPY AND ONCOLOGY
	2018
卷号	129 页码:84-94
关键词	Genistein DNA-PKcs Carbon ion radiotherapy Radiosensitization DSB repair
ISSN号	0167-8140
DOI	10.1016/j.radonc.2018.04.005
英文摘要	Background and purpose: Previously, we found genistein could sensitize cancer cells to low linear energy transfer (LET) X-rays via inhibiting DNA-PKcs activities. Especially, high-LET heavy ion produces more DNA double strand breaks (DSBs) than low-LET radiation. Thus, the study was designed to investigate the detailed molecular mechanisms of genistein on sensitizing cancer cells to heavy ions.Materials and methods: Human glioblastoma (GBM) cell lines with or without genistein pre-treatment were irradiated with high-LET carbon ions. Cell survival was determined with colony formation assay. DNA DSBs were evaluated by means of detecting c-H2AX foci and immuno-blotting DSB repair proteins, cell apoptosis was detected using Annexin V and PI staining. The interaction of genistein with DNA-PKcs activation site was estimated by molecular docking in the autodock software.Results: Genistein sensitized DNA-PKcs proficient GBM cells to high-LET carbon ions via delaying the clearance of c-H2AX foci. Genistein was physically bound to DNA-PKcs and functionally inhibited the phosphorylation of DNA-PKcs. Consequently, the non-homologous end joining (NHEJ) repair of DSBs was inhibited and the homologous recombination (HR) repair was delayed by genistein, thereby leading to an increase in apoptosis in DNA-PKcs proficient GBM cells after irradiation.Conclusion: Our study demonstrated that genistein holds promise as a radiosensitizer for enhancing the efficacy of carbon ion radiotherapy against DNA-PKcs proficient GBM via inhibiting DNA-PKcs phosphorylation and subsequently repressing NHEJ and delaying HR repair pathways. (C) 2018 Elsevier B. V. All rights reserved. Radiotherapy and Oncology
资助项目	Youth Innovation Promotion Association[2015340]
WOS关键词	DEPENDENT PROTEIN-KINASE ; DOUBLE-STRAND BREAKS ; HOMOLOGOUS RECOMBINATION ; END-RESECTION ; CANCER-CELLS ; IONIZING-RADIATION ; CATALYTIC SUBUNIT ; MAMMALIAN-CELLS ; DAMAGE ; CHOICE
WOS研究方向	Oncology ; Radiology, Nuclear Medicine & Medical Imaging
语种	英语
出版者	ELSEVIER IRELAND LTD
WOS记录号	WOS:000449458600013
内容类型	期刊论文
源URL	[http://119.78.100.186/handle/113462/59887]
专题	近代物理研究所_兰州重离子研究装置近代物理研究所_生物物理研究室
通讯作者	Li, Qiang
推荐引用方式 GB/T 7714	Liu, Xiongxiong,Li, Qiang,Zhao, Ting,et al. Genistein sensitizes glioblastoma cells to carbon ions via inhibiting DNA-PKcs phosphorylation and subsequently repressing NHEJ and delaying HR repair pathways[J]. RADIOTHERAPY AND ONCOLOGY,2018,129:84-94.
APA	Liu, Xiongxiong.,Li, Qiang.,Zhao, Ting.,Ye, Fei.,Zhang, Pengcheng.,...&Liu, Bingtao.(2018).Genistein sensitizes glioblastoma cells to carbon ions via inhibiting DNA-PKcs phosphorylation and subsequently repressing NHEJ and delaying HR repair pathways.RADIOTHERAPY AND ONCOLOGY,129,84-94.
MLA	Liu, Xiongxiong,et al."Genistein sensitizes glioblastoma cells to carbon ions via inhibiting DNA-PKcs phosphorylation and subsequently repressing NHEJ and delaying HR repair pathways".RADIOTHERAPY AND ONCOLOGY 129(2018):84-94.