PMID- 29436645 OWN - NLM STAT- MEDLINE DCOM- 20180827 LR - 20211204 IS - 1791-3004 (Electronic) IS - 1791-2997 (Print) IS - 1791-2997 (Linking) VI - 17 IP - 4 DP - 2018 Apr TI - Ouabain suppresses the growth and migration abilities of glioma U‑87MG cells through inhibiting the Akt/mTOR signaling pathway and downregulating the expression of HIF‑1alpha. PG - 5595-5600 LID - 10.3892/mmr.2018.8587 [doi] AB - Glioma is one of the most malignant forms of brain tumor, and has been of persistent concern due to its high recurrence and mortality rates, and limited therapeutic options. As a cardiac glycoside, ouabain has widespread applications in congestive heart diseases due to its positive cardiac inotropic effect by inhibiting Na+/K+‑ATPase. Previous studies have demonstrated that ouabain has antitumor activity in several types of human tumor, including glioma. However, the exact underlying mechanism remains to be elucidated. The purpose of present study was to elucidate the effect of ouabain on human glioma cell apoptosis and investigate the exact mechanism. U‑87MG cells were treated with various concentrations of ouabain for 24 h, following which cell viability and survival rate were assessed using a 3‑(4,5-dimethylthiazol-2‑yl)‑2,5‑diphenyltetrazolium bromide assay. The dynamic changes and cell motility were observed using digital holographic microscopy. Additionally, western blot analysis and high‑content screening assays were used to detect the protein expression levels of phosphorylated (p‑)Akt, mammalian target of rapamycin (mTOR), p‑mTOR and hypoxia‑inducible factor (HIF)‑1alpha, respectively. Compared with the control group, ouabain suppressed U‑87MG cell survival, and attenuated cell motility in a dose‑dependent manner (P<0.01). The downregulation of p‑Akt, mTOR, p‑mTOR and HIF‑1alpha were observed following treatment with 2.5 and 25 micromol/l of ouabain. These results suggested that ouabain exerted suppressive effects on tumor cell growth and motility, leading to cell death via regulating the intracellular Akt/mTOR signaling pathway and inhibiting the expression of HIF‑1alpha in glioma cells. The present study examined the mechanism underlying the antitumor property of ouabain, providing a novel potential therapeutic agent for glioma treatment. FAU - Yang, Xiao-Sa AU - Yang XS AD - Institute of TBI and Neuroscience of Chinese People's Armed Police Force, Tianjin Key Laboratory of Neurotrauma Repair, Center for Neurology and Neurosurgery of Affiliated Hospital of Logistics University of PAP, Tianjin 300162, P.R. China. FAU - Xu, Zhong-Wei AU - Xu ZW AD - Central Laboratory of Logistics University of PAP, Tianjin 300309, P.R. China. FAU - Yi, Tai-Long AU - Yi TL AD - Institute of TBI and Neuroscience of Chinese People's Armed Police Force, Tianjin Key Laboratory of Neurotrauma Repair, Center for Neurology and Neurosurgery of Affiliated Hospital of Logistics University of PAP, Tianjin 300162, P.R. China. FAU - Xu, Rui-Cheng AU - Xu RC AD - Tianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazard, Logistics University of PAP, Tianjin 300309, P.R. China. FAU - Li, Jie AU - Li J AD - Institute of TBI and Neuroscience of Chinese People's Armed Police Force, Tianjin Key Laboratory of Neurotrauma Repair, Center for Neurology and Neurosurgery of Affiliated Hospital of Logistics University of PAP, Tianjin 300162, P.R. China. FAU - Zhang, Wen-Bin AU - Zhang WB AD - Institute of TBI and Neuroscience of Chinese People's Armed Police Force, Tianjin Key Laboratory of Neurotrauma Repair, Center for Neurology and Neurosurgery of Affiliated Hospital of Logistics University of PAP, Tianjin 300162, P.R. China. FAU - Zhang, Sai AU - Zhang S AD - Institute of TBI and Neuroscience of Chinese People's Armed Police Force, Tianjin Key Laboratory of Neurotrauma Repair, Center for Neurology and Neurosurgery of Affiliated Hospital of Logistics University of PAP, Tianjin 300162, P.R. China. FAU - Sun, Hong-Tao AU - Sun HT AD - Institute of TBI and Neuroscience of Chinese People's Armed Police Force, Tianjin Key Laboratory of Neurotrauma Repair, Center for Neurology and Neurosurgery of Affiliated Hospital of Logistics University of PAP, Tianjin 300162, P.R. China. FAU - Yu, Ze-Qi AU - Yu ZQ AD - Institute of TBI and Neuroscience of Chinese People's Armed Police Force, Tianjin Key Laboratory of Neurotrauma Repair, Center for Neurology and Neurosurgery of Affiliated Hospital of Logistics University of PAP, Tianjin 300162, P.R. China. FAU - Xu, Hao-Xiang AU - Xu HX AD - Institute of TBI and Neuroscience of Chinese People's Armed Police Force, Tianjin Key Laboratory of Neurotrauma Repair, Center for Neurology and Neurosurgery of Affiliated Hospital of Logistics University of PAP, Tianjin 300162, P.R. China. FAU - Tu, Yue AU - Tu Y AD - Institute of TBI and Neuroscience of Chinese People's Armed Police Force, Tianjin Key Laboratory of Neurotrauma Repair, Center for Neurology and Neurosurgery of Affiliated Hospital of Logistics University of PAP, Tianjin 300162, P.R. China. FAU - Cheng, Shi-Xiang AU - Cheng SX AD - Institute of TBI and Neuroscience of Chinese People's Armed Police Force, Tianjin Key Laboratory of Neurotrauma Repair, Center for Neurology and Neurosurgery of Affiliated Hospital of Logistics University of PAP, Tianjin 300162, P.R. China. LA - eng PT - Journal Article DEP - 20180212 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 5ACL011P69 (Ouabain) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM EIN - Mol Med Rep. 2021 Mar;23(3):. PMID: 33495805 MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Cell Survival/drug effects MH - Gene Expression Regulation, Neoplastic/*drug effects MH - Glioma/*genetics/*metabolism/pathology MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/*genetics/metabolism MH - Ouabain/*pharmacology MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Signal Transduction/*drug effects MH - TOR Serine-Threonine Kinases/*metabolism PMC - PMC5865999 OTO - NOTNLM OT - ouabain OT - glioblastoma OT - U-87MG cells OT - Akt/mammalian target of rapamycin signaling pathway OT - hypoxia-inducible factor-1alpha EDAT- 2018/02/14 06:00 MHDA- 2018/08/28 06:00 PMCR- 2018/02/12 CRDT- 2018/02/14 06:00 PHST- 2016/09/30 00:00 [received] PHST- 2017/06/05 00:00 [accepted] PHST- 2018/02/14 06:00 [pubmed] PHST- 2018/08/28 06:00 [medline] PHST- 2018/02/14 06:00 [entrez] PHST- 2018/02/12 00:00 [pmc-release] AID - mmr-17-04-5595 [pii] AID - 10.3892/mmr.2018.8587 [doi] PST - ppublish SO - Mol Med Rep. 2018 Apr;17(4):5595-5600. doi: 10.3892/mmr.2018.8587. Epub 2018 Feb 12.