Meloxicam suppresses hepatocellular carcinoma cell proliferation and migration by targeting COX-2/PGE2-regulated activation of the β-catenin signaling pathway.

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dc.contributor.author Li, Tao en
dc.contributor.author Zhong, Jingtao en
dc.contributor.author Dong, Xiaofeng en
dc.contributor.author Xiu, Peng en
dc.contributor.author Wang, Fuhai en
dc.contributor.author Wei, Honglong en
dc.contributor.author Wang, Xin en
dc.contributor.author Xu, Zongzhen en
dc.contributor.author Liu, Feng en
dc.contributor.author Sun, Xueying en
dc.contributor.author Li, Jie en
dc.date.accessioned 2018-10-18T00:05:06Z en
dc.date.issued 2016-06 en
dc.identifier.citation Oncology reports 35(6):3614-3622 Jun 2016 en
dc.identifier.issn 1021-335X en
dc.identifier.uri http://hdl.handle.net/2292/42760 en
dc.description.abstract Recurrence and metastasis are the two leading causes of poor prognosis of hepatocellular carcinoma (HCC) patients. Cyclooxygenase (COX)-2 is overexpressed in many types of cancers including HCC and promotes its metastasis. Meloxicam is a selective COX-2 inhibitor that has been reported to exert an anti-proliferation and invasion/migration response in various tumors. In this study, we examined the role of meloxicam on HCC cell proliferation and migration and explored the molecular mechanisms underlying this effect. We found that meloxicam inhibited HCC cell proliferation and had a cell cycle arrest effect in human HCC cells. Furthermore, meloxicam suppressed the ability of HCC cells expressing higher levels of COX-2 and prostaglandin E2 (PGE2) to migration via potentiating expression of E-cadherin and alleviating expression of matrix metalloproteinase (MMP)-2 and -9. COX-2/PGE2 has been considered to activate the β-catenin signaling pathway which promotes cancer cell migration. We found that treatment with PGE2 significantly enhanced nuclear accumulation of β-catenin and the activation of GSK3β which could be reversed by meloxicam in HCC cells. We also observed that HCC cell migration and upregulation of the level of MMP-2/9 and downregulation of E-cadherin induced by PGE2 were suppressed by FH535, an inhibitor of β-catenin. Taken together, these findings provide a new treatment strategy against HCC proliferation and migration. en
dc.format.medium Print-Electronic en
dc.language eng en
dc.relation.ispartofseries Oncology 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://www.spandidos-publications.com/pages/info_for_authors_or en
dc.subject Cell Line, Tumor en
dc.subject Humans en
dc.subject Carcinoma, Hepatocellular en
dc.subject Liver Neoplasms en
dc.subject Neoplasm Invasiveness en
dc.subject Sulfonamides en
dc.subject Thiazines en
dc.subject Thiazoles en
dc.subject Dinoprostone en
dc.subject Cadherins en
dc.subject RNA, Small Interfering en
dc.subject Cyclooxygenase Inhibitors en
dc.subject Signal Transduction en
dc.subject Cell Proliferation en
dc.subject Cell Movement en
dc.subject Cell Survival en
dc.subject RNA Interference en
dc.subject Enzyme Activation en
dc.subject beta Catenin en
dc.subject Cyclooxygenase 2 en
dc.subject Matrix Metalloproteinase 2 en
dc.subject Matrix Metalloproteinase 9 en
dc.subject Hep G2 Cells en
dc.subject Cell Cycle Checkpoints en
dc.subject Glycogen Synthase Kinase 3 beta en
dc.title Meloxicam suppresses hepatocellular carcinoma cell proliferation and migration by targeting COX-2/PGE2-regulated activation of the β-catenin signaling pathway. en
dc.type Journal Article en
dc.identifier.doi 10.3892/or.2016.4764 en
pubs.issue 6 en
pubs.begin-page 3614 en
pubs.volume 35 en
dc.rights.holder Copyright: Spandidos Publications en
dc.identifier.pmid 27109804 en
pubs.end-page 3622 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.subtype Journal Article en
pubs.elements-id 532597 en
dc.identifier.eissn 1791-2431 en
pubs.record-created-at-source-date 2016-05-09 en
pubs.dimensions-id 27109804 en


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