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Genistein inhibits radiation-induced invasion and migration of glioblastoma cells by blocking the DNA-PKcs/Akt2/Rac1 signaling pathway

文献类型：期刊论文

作者Liu, Xiongxiong2,3,4,5; Wang, Qiqi1; Liu, Bingtao2,3,4,5; Zheng, Xiaogang2,3,4,5; Li, Ping2,3,4,5; Zhao, Ting2,3,4,5; Jin, Xiaodong2,3,4,5; Ye, Fei2,3,4,5; Zhang, Pengcheng2,3,4,5; Chen, Weiqiang2,3,4,5
刊名RADIOTHERAPY AND ONCOLOGY
出版日期2021-02-01
卷号155页码:93-104
ISSN号0167-8140
关键词Glioblastoma multiforme DNA-PKcs/Akt2/Rac1 signaling Genistein Radiation Invasion and migration
DOI10.1016/j.radonc.2020.10.026
通讯作者Li, Qiang(liqiang@impcas.ac.cn)
英文摘要Background and purpose: Radiotherapy is the most important therapeutic measure against glioblastoma multiforme (GBM), which is regarded as the most common and highly lethal type of brain cancer. Nevertheless, most relapses originate in the close vicinity of the irradiated target volume. Genistein is a natural product that can suppress the invasive potential of cancer cells. In this study, DNAdependent protein kinase catalytic subunit (DNA-PKcs)-proficient and -deficient GBM cells were selected for in vitro and in vivo studies to investigate the inhibiting effects of genistein on radiation-induced invasion and migration and the corresponding mechanism. Materials and methods: GBM cell lines with or without genistein pre-treatment were irradiated with X-rays. Cell survival was determined using colony formation assay and the rate of cellular proliferation was analyzed with a real-time cell electronic sensing system. For in vitro study, invasion and migration abilities were evaluated via wound-healing and transwell assays, while protein expression was determined with western blotting. Genistein interaction with DNA-PKcs was estimated with pull-down, recombinant and binding assays. For in vivo study, cells were stereotactically injected into NOD-SCID mice to establish tumors. Hematoxylin and eosin and immunohistochemistry were used to assess the invasive potential of GBM. Results: X-ray irradiation enhanced the migration and invasion of DNA-PKcs-positive but not DNA-PKcs-negative GBM cells. It also activated the DNA-PKcs/Akt2/Rac1 signaling pathway, which contributed to GBM malignant progression by aggravating GBM cell invasive potential. The study successfully demonstrated that genistein can specifically bind to DNA-PKcs and block the DNA-PKcs/Akt2/Rac1 pathway, thereby effectively inhibiting radiation-induced invasion and migration of GBM cells in vitro and in vivo. The present study emphasized that radiation-induced invasive potential is initiated by DNA-PKcs, which is a well-known double strand breaks (DSB) repair protein, and determined the exact site for genistein binding to DNA-PKcs. Conclusion: DNA-PKcs is not only a potential target for cancer therapy, but also a reliable biomarker for predicting radiation-induced invasion and migration of GBM cells. Thus, genistein might serve as a novel therapeutic strategy for treating GBM. (C) 2020 Elsevier B.V. All rights reserved.
资助项目National Key Research and Development Program of China[2018YFC0115700] ; National Key Research and Development Program of China[2018YFC0115702] ; National Natural Science Foundation of China[11705245] ; National Natural Science Foundation of China[11875299] ; National Natural Science Foundation of China[11775280] ; Key Deployment Project of Chinese Academy of Sciences[KFZD-SW-222] ; Western Talents Program of the Chinese Academy of Sciences[Y562020XB0] ; Western Talents Program of the Chinese Academy of Sciences[Y866020XB0] ; Fellow of Youth Innovation Promotion Association[2020414]
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:000628819400027
资助机构National Key Research and Development Program of China ; National Natural Science Foundation of China ; Key Deployment Project of Chinese Academy of Sciences ; Western Talents Program of the Chinese Academy of Sciences ; Fellow of Youth Innovation Promotion Association
源URL[http://119.78.100.186/handle/113462/137706]  
专题中国科学院近代物理研究所
通讯作者Li, Qiang
作者单位1.Northwest Normal Univ, Coll Life Sci, Lanzhou, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Key Lab Basic Res Heavy Ion Radiat Applicat Med, Lanzhou, Gansu, Peoples R China
4.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou, Gansu, Peoples R China
5.Chinese Acad Sci, Inst Modern Phys, 509 Nanchang Rd, Lanzhou 730000, Gansu, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Xiongxiong,Wang, Qiqi,Liu, Bingtao,et al. Genistein inhibits radiation-induced invasion and migration of glioblastoma cells by blocking the DNA-PKcs/Akt2/Rac1 signaling pathway[J]. RADIOTHERAPY AND ONCOLOGY,2021,155:93-104.
APA Liu, Xiongxiong.,Wang, Qiqi.,Liu, Bingtao.,Zheng, Xiaogang.,Li, Ping.,...&Li, Qiang.(2021).Genistein inhibits radiation-induced invasion and migration of glioblastoma cells by blocking the DNA-PKcs/Akt2/Rac1 signaling pathway.RADIOTHERAPY AND ONCOLOGY,155,93-104.
MLA Liu, Xiongxiong,et al."Genistein inhibits radiation-induced invasion and migration of glioblastoma cells by blocking the DNA-PKcs/Akt2/Rac1 signaling pathway".RADIOTHERAPY AND ONCOLOGY 155(2021):93-104.

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来源：近代物理研究所

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