Genistein sensitizes glioblastoma cells to carbon ions via inhibiting DNA-PKcs phosphorylation and subsequently repressing NHEJ and delaying HR repair pathways
文献类型：期刊论文
| 作者 | Liu, Xiongxiong; Li, Qiang ; Zhao, Ting; Ye, Fei; Zhang, Pengcheng; Jin, Xiaodong; Chen, Weiqiang; Liu, Xinguo; Niu, Yuzhen; Hirayama, Ryoichi
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| 刊名 | RADIOTHERAPY AND ONCOLOGY
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| 出版日期 | 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 |
| WOS关键词 | DEPENDENT PROTEIN-KINASE ; DOUBLE-STRAND BREAKS ; HOMOLOGOUS RECOMBINATION ; END-RESECTION ; CANCER-CELLS ; IONIZING-RADIATION ; CATALYTIC SUBUNIT ; MAMMALIAN-CELLS ; DAMAGE ; CHOICE |
| 资助项目 | Youth Innovation Promotion Association[2015340] |
| WOS研究方向 | Oncology ; Radiology, Nuclear Medicine & Medical Imaging |
| 语种 | 英语 |
| WOS记录号 | WOS:000449458600013 |
| 出版者 | ELSEVIER IRELAND LTD |
| 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. |
入库方式： OAI收割
来源：近代物理研究所
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