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Disruption of Chromosomal Architecture of cox2 Locus Sensitizes Lung Cancer Cells to Radiotherapy

文献类型：期刊论文

作者Sun, Yuxiang1,3; Dai, Hui1,3,4; Chen, Shaopeng1,3; Zhang, Yajun1,3,4; Wu, Tao1,3,4; Cao, Xianbin1,3,4; Zhao, Guoping1,3; Xu, An1,2,3; Wang, Jun1,3; Wu, Lijun1,2,3
刊名MOLECULAR THERAPY
出版日期2018-10-03
卷号26期号:10页码:2456-2465
ISSN号1525-0016
DOI10.1016/j.ymthe.2018.08.002
通讯作者Chen, Shaopeng(spchen035@ipp.ac.cn) ; Wu, Lijun(ljw@ipp.ac.cn)
英文摘要Despite treatment of lung cancer with radiotherapy and chemotherapy, the survival rate of lung cancer patients remains poor. Previous studies demonstrated the importance of upregulation of inflammatory factors, such as cyclooxygenase 2 (cox2), in tumor tolerance. In the present study, we investigated the role of cox2 in radiosensitivity of lung cancer. Our results showed that the combination treatment of radiation with aspirin, an anti-inflammatory drug, induced a synergistic reduction of cell survival in A549 and H1299 lung cancer cells. In comparison with normal human lung fibroblasts (NHLFs), the cell viability was significantly decreased and the level of apoptosis was remarkably enhanced in A549 cells. Mechanistic studies revealed that the reduction of cox2 by aspirin in A549 and H1299 was caused by disruption of the chromosomal architecture of the cox2 locus. Moreover, the disruption of chromatin looping was mediated by the inhibition of nuclear translocation of p65 and decreased enrichment of p65 at cox2-regulatory elements. Importantly, disorganization of the chromosomal architecture of cox2 triggered A549 cells sensitive to g-radiation by the induction of apoptosis. In conclusion, we present evidence of an effective therapeutic treatment targeting the epigenetic regulation of lung cancer and a potential strategy to overcome radiation resistance in cancer cells.
WOS关键词RADIATION-RESISTANCE ; GENE-TRANSCRIPTION ; INDUCED APOPTOSIS ; PROSTATE-CANCER ; BREAST-CANCER ; CHROMATIN ; ASPIRIN ; CYCLOOXYGENASE-2 ; EXPRESSION ; THERAPY
资助项目National Natural Science Foundation of China[31470829] ; National Natural Science Foundation of China[81273004] ; National Basic Research 973 Program[2014CB932002] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB14030502]
WOS研究方向Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine
语种英语
WOS记录号WOS:000447758800014
出版者CELL PRESS
资助机构National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Basic Research 973 Program ; National Basic Research 973 Program ; National Basic Research 973 Program ; National Basic Research 973 Program ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Basic Research 973 Program ; National Basic Research 973 Program ; National Basic Research 973 Program ; National Basic Research 973 Program ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Basic Research 973 Program ; National Basic Research 973 Program ; National Basic Research 973 Program ; National Basic Research 973 Program ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Basic Research 973 Program ; National Basic Research 973 Program ; National Basic Research 973 Program ; National Basic Research 973 Program ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/39384]  
专题中国科学院合肥物质科学研究院
通讯作者Chen, Shaopeng; Wu, Lijun
作者单位1.Chinese Acad Sci, Hefei Inst Phys Sci, Key Lab High Magnet Field & Ion Beam Phys Biol, Hefei 230031, Anhui, Peoples R China
2.Anhui Univ, Inst Phys Sci & Informat Technol, Hefei 230601, Anhui, Peoples R China
3.Key Lab Environm Toxicol & Pollut Control Technol, Hefei 230031, Anhui, Peoples R China
4.Univ Sci & Technol China, Hefei 230026, Anhui, Peoples R China
推荐引用方式
GB/T 7714		 Sun, Yuxiang,Dai, Hui,Chen, Shaopeng,et al. Disruption of Chromosomal Architecture of cox2 Locus Sensitizes Lung Cancer Cells to Radiotherapy[J]. MOLECULAR THERAPY,2018,26(10):2456-2465.
APA Sun, Yuxiang.,Dai, Hui.,Chen, Shaopeng.,Zhang, Yajun.,Wu, Tao.,...&Wu, Lijun.(2018).Disruption of Chromosomal Architecture of cox2 Locus Sensitizes Lung Cancer Cells to Radiotherapy.MOLECULAR THERAPY,26(10),2456-2465.
MLA Sun, Yuxiang,et al."Disruption of Chromosomal Architecture of cox2 Locus Sensitizes Lung Cancer Cells to Radiotherapy".MOLECULAR THERAPY 26.10(2018):2456-2465.

入库方式： OAI收割

来源：合肥物质科学研究院

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