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, Xiongxiong1,2,3; Li, Ping1,2,3; Hirayama, Ryoichi4; Niu, Yuzhen5; Liu, Xinguo1,2,3; Chen, Weiqiang1,2,3; Jin, Xiaodong1,2,3; Zhang, Pengcheng1,2,3,6; Ye, Fei1,2,3; Zhao, Ting1,2,3 |
| 刊名 | RADIOTHERAPY AND ONCOLOGY
 |
| 出版日期 | 2018-10-01 |
| 卷号 | 129期号:1页码:84-94 |
| ISSN号 | 0167-8140 |
| 关键词 | Genistein DNA-PKcs Carbon ion radiotherapy Radiosensitization DSB repair |
| DOI | 10.1016/j.radonc.2018.04.005 |
| 通讯作者 | Li, Qiang(liqiang@impcas.ac.cn) |
| 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 |
| 收录类别 | SCI |
| 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 |
| WOS类目 | Oncology ; Radiology, Nuclear Medicine & Medical Imaging |
| 语种 | 英语 |
| 出版者 | ELSEVIER IRELAND LTD |
| WOS记录号 | WOS:000449458600013 |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2558259 |
| 专题 | 寒区旱区环境与工程研究所 |
| 通讯作者 | Li, Qiang |
| 作者单位 | 1.Chinese Acad Sci, Inst Modern Phys, 509 Nanchang Rd, Lanzhou 730000, Gansu, Peoples R China 2.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou, Gansu, Peoples R China 3.Key Lab Basic Res Heavy Ion Radiat Applicat Med, Lanzhou, Gansu, Peoples R China 4.Natl Inst Radiol Sci, Res Ctr Charged Particle Therapy, Chiba, Japan 5.Shandong Univ Technol, Shandong Prov Res Ctr Bioinformat Engn & Tech, Sch Life Sci, Zibo, Peoples R China 6.Univ Chinese Acad Sci, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Xiongxiong,Li, Ping,Hirayama, Ryoichi,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(1):84-94. |
| APA | Liu, Xiongxiong.,Li, Ping.,Hirayama, Ryoichi.,Niu, Yuzhen.,Liu, Xinguo.,...&Li, Qiang.(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(1),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 129.1(2018):84-94. |
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来源：寒区旱区环境与工程研究所
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