Sodium orthovanadate overcomes sorafenib resistance of hepatocellular carcinoma cells by inhibiting Na+/K+-ATPase activity and hypoxia-inducible pathways.

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dc.contributor.author Jiang, Wenjing en
dc.contributor.author Li, Guangxin en
dc.contributor.author Li, Weidong en
dc.contributor.author Wang, Ping en
dc.contributor.author Xiu, Peng en
dc.contributor.author Jiang, Xian en
dc.contributor.author Liu, Bing en
dc.contributor.author Sun, Xueying en
dc.contributor.author Jiang, Hongchi en
dc.date.accessioned 2020-05-07T03:37:12Z en
dc.date.issued 2018-06-26 en
dc.identifier.citation Scientific reports 8(1):9706 26 Jun 2018 en
dc.identifier.issn 2045-2322 en
dc.identifier.uri http://hdl.handle.net/2292/50550 en
dc.description.abstract The resistance to sorafenib highly affects its clinical benefits for treating hepatocellular carcinoma (HCC). Sodium orthovanadate (SOV) is a phosphate analog that displays anti-cancer activities against various types of malignancies including HCC. The present study has demonstrated that SOV is able to overcome sorafenib resistance and strengthens sorafenib in suppressing sorafenib-resistant HCC cells in vitro and in animal models. Similar to its action on parental HCC cells, SOV induced cell cycle arrest at G2/M phases by regulating cyclin B1 and cyclin-dependent kinase 1, and apoptosis by reducing mitochondrial membrane potential, in sorafenib-resistant HCC cells. More importantly, SOV inhibited ATPase activity, which was significantly elevated in sorafenib-resistant HCC cells. SOV also reduced the expression of HIF-1α and HIF-2α and their nuclear translocation, resulting in downregulation of their downstream factors including vascular endothelial growth factor, lactate dehydrogenase-A and glucose transporter 1. Its ability to inhibit ATPase activity and hypoxia-inducible pathways enabled SOV to efficiently suppress both normoxic and hypoxic cells, which compose cancer cell populations inside sorafenib-resistant HCC tumors. The present results indicate that SOV may be a potent candidate drug for overcoming the resistance to sorafenib in treating HCC. en
dc.format.medium Electronic en
dc.language eng en
dc.relation.ispartofseries Scientific reports en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri https://creativecommons.org/licenses/by/4.0/ en
dc.subject Cell Line, Tumor en
dc.subject Animals en
dc.subject Mice, Inbred BALB C en
dc.subject Humans en
dc.subject Mice en
dc.subject Carcinoma, Hepatocellular en
dc.subject Liver Neoplasms en
dc.subject Vanadates en
dc.subject Isoenzymes en
dc.subject L-Lactate Dehydrogenase en
dc.subject Vascular Endothelial Growth Factor A en
dc.subject Antineoplastic Agents en
dc.subject Apoptosis en
dc.subject Cell Proliferation en
dc.subject Cell Hypoxia en
dc.subject Gene Expression Regulation, Neoplastic en
dc.subject Drug Resistance, Neoplasm en
dc.subject Male en
dc.subject Glucose Transporter Type 1 en
dc.subject Adenosine Triphosphatases en
dc.subject Sorafenib en
dc.title Sodium orthovanadate overcomes sorafenib resistance of hepatocellular carcinoma cells by inhibiting Na+/K+-ATPase activity and hypoxia-inducible pathways. en
dc.type Journal Article en
dc.identifier.doi 10.1038/s41598-018-28010-y en
pubs.issue 1 en
pubs.begin-page 9706 en
pubs.volume 8 en
dc.rights.holder Copyright: The authors en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.subtype Research Support, Non-U.S. Gov't en
pubs.subtype research-article en
pubs.subtype Journal Article en
pubs.elements-id 747168 en
dc.identifier.eissn 2045-2322 en
pubs.record-created-at-source-date 2018-06-28 en
pubs.dimensions-id 29946188 en


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