Sodium chloride (NaCl) potentiates digoxin-induced anti-tumor activity in small cell lung cancer | |
Deng, Ke1,4,5; Shen, Jiawei2; Wang, Wei4,5; Li, Ming1,3,4,5; Li, Hong4,5; Chen, Cheng1,4,5; Zhao, Huan2,6; Zhang, Mei2; Xue, Tian2; Liu, Qingsong4,5 | |
刊名 | CANCER BIOLOGY & THERAPY |
2019-01-02 | |
卷号 | 20期号:1页码:52-64 |
关键词 | small cell lung cancer digoxin NaCl cardiac glycosides ATP1A1 |
ISSN号 | 1538-4047 |
DOI | 10.1080/15384047.2018.1504723 |
英文摘要 | Small cell lung cancer (SCLC) is a malignant neuroendocrine tumor with very high mortality. Effective new therapy for advanced SCLC patients is urgently needed. By screening a FDA-approved drug library, we identified a cardiac glycoside (CG), namely digoxin (an inhibitor of cellular Na+/K+ ATPase pump), which was highly effective in inhibiting SCLC cell growth. Intriguing findings showed that NaCl supplement markedly enhanced the anti-tumor activities of digoxin in both in vitro and in vivo models of SCLC. Subsequent analysis revealed that this novel combination of digoxin/NaCl caused an up-regulation of intracellular Na+ and Ca2+ levels with an induction of higher resting membrane potential of SCLC cells. We also found that this combination lead to morphological shrinking of SCLC cells, together with high levels of cytochrome C release. Lastly, our data revealed that NaCl supplement was able to induce the expression of ATP1A1 (a Na+/K+ ATPase subunit), in which contributes directly to the increased sensitivity of SCLC cells to digoxin. Thus, this is the first demonstration that NaCl is a potent supplement necessitating superior anti-cancer effects of digoxin for SCLC. Further, our study suggests that digoxin treatment could need to be combined with NaCl supplement in future clinical trial of SCLC, particularly where low Na+ is often present in SCLC patients. |
资助项目 | National Natural Science Foundation of China[81502632] ; National Natural Science Foundation of China[81372214] ; National Natural Science Foundation of China[31601134] ; National Natural Science Foundation of China[61727811] ; Natural Science Foundation of Anhui Province[1608085MH179] ; Natural Science Foundation of Anhui Province[1708085QC57] ; Key Technologies R&D Program of Anhui Province[1604a0802103] ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology[2016FXCX006] ; Research Grant Council, Hong Kong[17114814] ; Research Grant Council, Hong Kong[17121616] ; Research Grant Council, Hong Kong[T12-401/13-R] ; [ZT00102901] |
WOS关键词 | CARDIAC-GLYCOSIDES ; HYPONATREMIA |
WOS研究方向 | Oncology |
语种 | 英语 |
出版者 | TAYLOR & FRANCIS INC |
WOS记录号 | WOS:000454533100008 |
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 Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; 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 Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; 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 Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; 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 Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Natural Science Foundation of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Key Technologies R&D Program of Anhui Province ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong ; Research Grant Council, Hong Kong |
内容类型 | 期刊论文 |
源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/41279] |
专题 | 合肥物质科学研究院_中科院强磁场科学中心 |
通讯作者 | Hong, Bo; Lin, Wenchu |
作者单位 | 1.Univ Sci & Technol China, Hefei, Anhui, Peoples R China 2.Univ Sci & Technol China, Sch Life Sci, Hefei, Anhui, Peoples R China 3.Univ Sci & Technol China, Dept Lab Diagnost, Western Branch, Affiliated Hosp 1, Hefei, Anhui, Peoples R China 4.Chinese Acad Sci, High Magnet Field Lab, Hefei, Anhui, Peoples R China 5.Chinese Acad Sci, Key Lab High Magnet Field & Ion Beam Phys Biol, Hefei Inst Phys Sci, Hefei, Anhui, Peoples R China 6.Hefei Univ, Dept Biol & Environm Engn, Hefei, Anhui, Peoples R China 7.Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Hong Kong, Peoples R China |
推荐引用方式 GB/T 7714 | Deng, Ke,Shen, Jiawei,Wang, Wei,et al. Sodium chloride (NaCl) potentiates digoxin-induced anti-tumor activity in small cell lung cancer[J]. CANCER BIOLOGY & THERAPY,2019,20(1):52-64. |
APA | Deng, Ke.,Shen, Jiawei.,Wang, Wei.,Li, Ming.,Li, Hong.,...&Lin, Wenchu.(2019).Sodium chloride (NaCl) potentiates digoxin-induced anti-tumor activity in small cell lung cancer.CANCER BIOLOGY & THERAPY,20(1),52-64. |
MLA | Deng, Ke,et al."Sodium chloride (NaCl) potentiates digoxin-induced anti-tumor activity in small cell lung cancer".CANCER BIOLOGY & THERAPY 20.1(2019):52-64. |
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