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 |
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pubs.volume |
8 |
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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 |