DNA-PKcs Inhibition Sensitizes Cancer Cells to Carbon-Ion Irradiation via Telomere Capping Disruption
文献类型：期刊论文
| 作者 | Zhou, Xin1,2,3 ; Zhang, Xin1,2,3; Xie, Yi1,2,3; Tanaka, Kaoru4; Wang, Bing4; Zhang, Hong1,2,3
|
| 刊名 | PLOS ONE
 |
| 出版日期 | 2013-08-27 |
| 卷号 | 8 |
| ISSN号 | 1932-6203 |
| DOI | 10.1371/journal.pone.0072641 |
| 文献子类 | Article |
| 英文摘要 | Heavy-ion irradiation induces a higher frequency of DNA double strand breaks (DSBs) which must be properly repaired. Critical shortening of telomeres can trigger DNA damage responses such as DSBs. Telomeres are very sensitive to oxidative stress such as ionizing radiation. The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is the central component in the non-homologous end joining (NHEJ) repair complex and participates in telomere maintenance. Therefore, it is expected to enhance the cell killing effect of heavy-ion irradiation via DNA-PKcs inhibition. To test this hypothesis, cellular radiosensitivity was measured by the clonal genetic assay. DNA damage repair was relatively quantified by long PCR. Apoptosis was quantified by flow-cytometric analysis of annexin V/PI double staining, and senescence was analyzed by galactosidase activity. Telomere length was semi-quantified by real-time PCR. P53 and p21 expression was determined by western blotting. Our data demonstrated that MCF-7 and HeLa cells with DNA-PKcs inhibition were more susceptible to carbon-ion irradiation than Those without DNA-PKcs inhibition. Even though NHEJ was inhibited by the DNA-PKcs specific inhibitor, NU7026, most DNA damage induced by carbon-ion irradiation was repaired within 24 hours after irradiation in both cell lines. However, potential lethal damage repair (PLDR) could not restore cellular inactivation in DNA-PKcs inhibited cells. MCF-7 cells showed extensive senescence and accelerated telomere length reduction, while HeLa cells underwent significant apoptosis after irradiation with NU7026 incubation. In addition, both cell lines with shorter telomere were more susceptible to carbon-ion radiation. Our current data suggested that DNA-PKcs inhibition could enhance cellular sensitivity to carbon-ion radiation via disturbing its functional role in telomere end protection. The combination of DNA-PKcs inhibition and carbon-ion irradiation may be an efficient method of heavy-ion therapy. |
| WOS关键词 | DOUBLE-STRAND BREAKS ; IONIZING-RADIATION ; HOMOLOGOUS RECOMBINATION ; REPAIR ; MAINTENANCE ; INSTABILITY ; DYSFUNCTION ; STRESS ; NBS1 |
| 资助项目 | National Institute of Radiological Sciences[11J364] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000323815200051 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 源URL | [http://119.78.100.186/handle/113462/48477]  |
| 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 Heavy Ion Radiat Med, Lanzhou, Peoples R China 2.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou, Peoples R China 3.Key Lab Heavy Ion Radiat Med Gansu Prov, Lanzhou, Peoples R China 4.Natl Inst Radiol Sci, Res Ctr Radiat Protect, Radiat Risk Reduct Res Program, Inage Ku, Chiba 260, Japan |
| 推荐引用方式 GB/T 7714 | Zhou, Xin,Zhang, Xin,Xie, Yi,et al. DNA-PKcs Inhibition Sensitizes Cancer Cells to Carbon-Ion Irradiation via Telomere Capping Disruption[J]. PLOS ONE,2013,8. |
| APA | Zhou, Xin,Zhang, Xin,Xie, Yi,Tanaka, Kaoru,Wang, Bing,&Zhang, Hong.(2013).DNA-PKcs Inhibition Sensitizes Cancer Cells to Carbon-Ion Irradiation via Telomere Capping Disruption.PLOS ONE,8. |
| MLA | Zhou, Xin,et al."DNA-PKcs Inhibition Sensitizes Cancer Cells to Carbon-Ion Irradiation via Telomere Capping Disruption".PLOS ONE 8(2013). |
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。