DNA-PKcs Deficiency Inhibits Glioblastoma Cell-Derived Angiogenesis After Ionizing Radiation
文献类型：期刊论文
| 作者 | Liu, Yang1,2,3 ; Zhang, Luwei1,2,3; Liu, Yuanyuan1,2,3; Sun, Chao1,2,3; Zhang, Hong1,2,3; Miao, Guoying1,4; Di, Cui Xia1,2,3; Zhou, Xin1,2,3; Zhou, Rong1,2,3; Wang, Zhenhua1,2,3
|
| 刊名 | JOURNAL OF CELLULAR PHYSIOLOGY
 |
| 出版日期 | 2015-05-01 |
| 卷号 | 230页码:1094-1103 |
| ISSN号 | 0021-9541 |
| DOI | 10.1002/jcp.24841 |
| 文献子类 | Article |
| 英文摘要 | DNA-dependent protein kinase catalytic subunit (DNA-PKcs) plays a critical role in non-homologous end-joining repair of DNA double-strand breaks (DSB) induced by ionizing radiation (IR). Little is known, however, regarding the relationship between DNA-PKcs and IR-induced angiogenesis; thus, in this study we aimed to further elucidate this relationship. Our findings revealed that lack of DNA-PKcs expression or activity sensitized glioma cells to radiation due to the defective DNA DSB repairs and inhibition of phosphorylated Akt(Ser473). Moreover, DNA-PKcs deficiency apparently mitigated IR-induced migration, invasion and tube formation of human microvascular endothelial cell (HMEC-1) in conditioned media derived from irradiated DNA-PKcs mutant M059J glioma cells or M059K glioma cells that have inhibited DNA-PKcs kinase activity due to the specific inhibitor NU7026 or siRNA knockdown. Moreover, IR-elevated vascular endothelial growth factor (VEGF) secretion was abrogated by DNA-PKcs suppression. Supplemental VEGF antibody to irradiated-conditioned media was negated enhanced cell motility with a concomitant decrease in phosphorylation of the FAK(Try925) and Src(Try416). Furthermore, DNA-PKcs suppression was markedly abrogated in IR-induced transcription factor hypoxia inducible factor-1 (HIF-1) accumulation, which is related to activation of VEGF transcription. These findings, taken together, demonstrate that depletion of DNA-PKcs in glioblastoma cells at least partly suppressed IR-inflicted migration, invasion, and tube formation of HMEC-1 cells, which may be associated with the reduced HIF-1 level and VEGF secretion. Inhibition of DNA-PKcs may be a promising therapeutic approach to enhance radio-therapeutic efficacy for glioblastoma by hindering its angiogenesis. J. Cell. Physiol. 230: 1094-1103, 2015. (c) 2014 Wiley Periodicals, Inc., A Wiley Company |
| WOS关键词 | DEPENDENT PROTEIN-KINASE ; ENDOTHELIAL GROWTH-FACTOR ; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA ; CARBON ION IRRADIATION ; MALIGNANT GLIOMA-CELLS ; IN-VIVO ; TUMOR-CELLS ; CONDITIONED MEDIUM ; PHOSPHATASE 6 ; CANCER-CELLS |
| 资助项目 | Scientific Technology Research Projects of Gansu Province[0702NKDA045] ; Scientific Technology Research Projects of Gansu Province[0806RJYA020] |
| WOS研究方向 | Cell Biology ; Physiology |
| 语种 | 英语 |
| WOS记录号 | WOS:000349301000014 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://119.78.100.186/handle/113462/50033]  |
| 专题 | 中国科学院近代物理研究所 |
| 通讯作者 | Zhang, Hong |
| 作者单位 | 1.Chinese Acad Sci, Inst Modern Phys, Dept Radiat Med, Lanzhou 730000, Peoples R China 2.Key Lab Heavy Ion Radiat Med Gansu Prov, Lanzhou, Peoples R China 3.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou 730000, Peoples R China 4.Chinese Acad Sci, Grad Sch, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Yang,Zhang, Luwei,Liu, Yuanyuan,et al. DNA-PKcs Deficiency Inhibits Glioblastoma Cell-Derived Angiogenesis After Ionizing Radiation[J]. JOURNAL OF CELLULAR PHYSIOLOGY,2015,230:1094-1103. |
| APA | Liu, Yang.,Zhang, Luwei.,Liu, Yuanyuan.,Sun, Chao.,Zhang, Hong.,...&Wang, Zhenhua.(2015).DNA-PKcs Deficiency Inhibits Glioblastoma Cell-Derived Angiogenesis After Ionizing Radiation.JOURNAL OF CELLULAR PHYSIOLOGY,230,1094-1103. |
| MLA | Liu, Yang,et al."DNA-PKcs Deficiency Inhibits Glioblastoma Cell-Derived Angiogenesis After Ionizing Radiation".JOURNAL OF CELLULAR PHYSIOLOGY 230(2015):1094-1103. |
入库方式： OAI收割
来源：近代物理研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。