Knockdown of Apolipoprotein E Enhanced Sensitivity of Hep3B Cells to Cardiac Steroids via Regulating Na+/K+-ATPase Signalosome
文献类型:期刊论文
作者 | Liu, Miao1; Feng, Li-Xing1; Sun, Peng1; Liu, Wang1; Mi, Tian1; Lei, Min2; Wu, Wanying1; Jiang, Baohong1; Yang, Min1; Hu, Lihong2 |
刊名 | MOLECULAR CANCER THERAPEUTICS |
出版日期 | 2016-12 |
卷号 | 15期号:12页码:2955-2965 |
ISSN号 | 1535-7163 |
DOI | 10.1158/1535-7163.MCT-15-0961 |
文献子类 | Article |
英文摘要 | This study compared the sensitivity of human hepatoma Hep3B, SK-HEP-1, SMMC-7721, and BEL-7402 cells to cardiac steroids, including bufalin (BF), a bufalin derivative (BF211), ouabain (OUA), and digitoxin (DIG). Hep3B cells exhibited relatively low sensitivity to cardiac steroids. Expression levels of subunits of Na+/K+-ATPase were high in Hep3B cells. However, colocalization of Na+/K+-ATPase and caveolin was nearly undetectable in Hep3B cells. By using RNA-Seq technology, we found a total of 36 genes to be differentially expressed between Hep3B cells and SK-HEP-1 cells, which are highly sensitive to cardiac steroids. Our bioinformatics analysis determined that these genes were mostly comprised of extracellular space, protein binding, and extracellular region. Among these 36 genes, apolipoprotein E(APOE) played a critical role, as knockdown APOE expression induced colocalization of Na+/K+-ATPase and caveolin and increased sensitivity of Hep3 cells to both proliferation-inhibiting and cytotoxic effects of BF or BF211. Also, the effects of BF on PI3K/AKT/GSK3 beta and apoptosis signal cascades were enhanced in APOE knockdown cells. The results of our study confirmed the role of Na+/K+-ATPase signalosome in cytotoxicity of cardiac steroids and suggested that APOE regulated the sensitivity of cells to cardiac steroids by affecting formation and function of Na+/K+-ATPase signalosome. In addition, intercellular interaction with high level of Na+/K+-ATPase beta 1 subunit may be also a factor in the low sensitivity of Hep3B cells to cardiac steroids. (C) 2016 AACR. |
WOS关键词 | HEPATOCELLULAR-CARCINOMA CELLS ; CANCER-CELLS ; LUNG-CANCER ; APOPTOSIS ; BUFALIN ; GLYCOSIDES ; SUBUNIT ; TRANSDUCTION ; DERIVATIVES ; EXPRESSION |
资助项目 | Shanghai Science & Technology Support Program[13431900401] ; Shanghai Science & Technology Innovation Action Program[15140904800] ; National Nature Science Foundation of China[81373964] ; National Science & Technology Major Project of China[2014ZX09301-306-03] |
WOS研究方向 | Oncology |
语种 | 英语 |
出版者 | AMER ASSOC CANCER RESEARCH |
WOS记录号 | WOS:000390092800014 |
源URL | [http://119.78.100.183/handle/2S10ELR8/275781] |
专题 | 上海中药现代化研究中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
通讯作者 | Hu, Lihong; Guo, De-An; Liu, Xuan |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Res Ctr Modernizat TCM, Shanghai, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China; 3.Shanghai Jiao Tong Univ, Sch Med, Shanghai Renji Hosp, Dept Cardiol, Shanghai, Peoples R China |
推荐引用方式 GB/T 7714 | Liu, Miao,Feng, Li-Xing,Sun, Peng,et al. Knockdown of Apolipoprotein E Enhanced Sensitivity of Hep3B Cells to Cardiac Steroids via Regulating Na+/K+-ATPase Signalosome[J]. MOLECULAR CANCER THERAPEUTICS,2016,15(12):2955-2965. |
APA | Liu, Miao.,Feng, Li-Xing.,Sun, Peng.,Liu, Wang.,Mi, Tian.,...&Liu, Xuan.(2016).Knockdown of Apolipoprotein E Enhanced Sensitivity of Hep3B Cells to Cardiac Steroids via Regulating Na+/K+-ATPase Signalosome.MOLECULAR CANCER THERAPEUTICS,15(12),2955-2965. |
MLA | Liu, Miao,et al."Knockdown of Apolipoprotein E Enhanced Sensitivity of Hep3B Cells to Cardiac Steroids via Regulating Na+/K+-ATPase Signalosome".MOLECULAR CANCER THERAPEUTICS 15.12(2016):2955-2965. |
入库方式: OAI收割
来源:上海药物研究所
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