机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and YunnanProvince, Kunming Institute of Zoology, Chinese Academy of Sciences/Key Laboratory of Bioactive Peptidesof Yunnan Province, Kunming 650223, Yunnan, China[2]Kunming College of Life Science, University of ChineseAcademy of Sciences, Kunming 650204, Yunnan, China[3]College of Life Sciences, Sichuan University, Chengdu610064, Sichuan, China[4]Stake Key Laboratory of Drug Research, The National Center for Drug Screening,Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China[5]Department ofNeurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China[6]CAS Center for Excellence in AnimalEvolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China[7]Kunming Key Laboratory ofHealthy Aging Molecular Mechanism Study, Kunming 650223, Yunnan, China
出处：
ISSN：
摘要：
Glioblastoma (GBM) is the most frequent brain cancer with poor prognosis and few therapies and urgently requires effective treatments. Na+/K+-ATPase is considered as a target for GBM therapy and development of anticancer drugs. Cardiac glycosides bind the Na+/K+-ATPase α subunit to inhibit enzymatic activity and are promising candidates for anticancer drug development including GBM. However, the comparatively higher doses required for effective anticancer actions cause severe cardiotoxicity. Selectively targeting the ATPase Na+/K+ transporting subunit beta 2 (ATP1B2) that is not expressed in the heart might avoid the cardiotoxicity. However, the effect of targeting ATP1B2 in GBM remains unknown. In this study, we found that high ATP1B2 expression is significantly associated with poor prognosis of patients with GBM. ATP1B2 silencing in GBM cells resulted in remarkably cell cycle arrest at the G2/M phase and apoptosis with concomitant increase in intracellular Ca2+ and activation of p38 kinase, similar to Na+/K+-ATPase inhibition by the classic cardiac glycoside digoxin. ATP1B2 is expressed higher in glioblastoma stem-like cells (GSCs) than in GBM cells and its downregulation induces apoptosis of GSCs. Furthermore, inducible ATP1B2 knockdown significantly inhibit tumor growth in vivo. Our data suggest ATP1B2 has potential as a therapeutic target for GBM.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|2 区医学
小类|3 区肿瘤学
最新[2025]版：
大类|3 区医学
小类|4 区肿瘤学
第一作者：
第一作者机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and YunnanProvince, Kunming Institute of Zoology, Chinese Academy of Sciences/Key Laboratory of Bioactive Peptidesof Yunnan Province, Kunming 650223, Yunnan, China[2]Kunming College of Life Science, University of ChineseAcademy of Sciences, Kunming 650204, Yunnan, China
共同第一作者：
通讯作者：
通讯机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and YunnanProvince, Kunming Institute of Zoology, Chinese Academy of Sciences/Key Laboratory of Bioactive Peptidesof Yunnan Province, Kunming 650223, Yunnan, China[6]CAS Center for Excellence in AnimalEvolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China[7]Kunming Key Laboratory ofHealthy Aging Molecular Mechanism Study, Kunming 650223, Yunnan, China[*1]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, 32 East Jiaochang Road, Kunming 650223, Yunnan, China
推荐引用方式(GB/T 7714)：
Li Shirong,Dai Zhi,Yang Dong,et al.Targeting β2 subunit of Na+/K+-ATPase induces glioblastoma cell apoptosis through elevation of intracellular Ca2.[J].American journal of cancer research.2019,9(6):1293-1308.
APA：
Li Shirong,Dai Zhi,Yang Dong,Li Wenxuan,Dai Hongjuan...&Zhao Xudong.(2019).Targeting β2 subunit of Na+/K+-ATPase induces glioblastoma cell apoptosis through elevation of intracellular Ca2..American journal of cancer research,9,(6)
MLA：
Li Shirong,et al."Targeting β2 subunit of Na+/K+-ATPase induces glioblastoma cell apoptosis through elevation of intracellular Ca2.".American journal of cancer research 9..6(2019):1293-1308
