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Article: Inhibition of mTOR enhances chemosensitivity in hepatocellular carcinoma

TitleInhibition of mTOR enhances chemosensitivity in hepatocellular carcinoma
Authors
KeywordsChemoresistance
Chemosensitivity
HCC
mTOR
p53
RAD001
Issue Date2009
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet
Citation
Cancer Letters, 2009, v. 273 n. 2, p. 201-209 How to Cite?
AbstractThe present study investigated the effect of mammalian target of rapamycin (mTOR) inhibition on HCC cells in vitro and in vivo, either alone or in combination with cytotoxic agents. In vitro, HCC cell lines were exposed to RAD001, an mTOR inhibitor, either alone or in combination with cisplatin. Alone, RAD001 suppressed cell proliferation in all cell lines tested, but did not induce apoptosis. RAD001 in combination with cisplatin induced a significant increase in the number of apoptotic cells, downregulated the expression of pro-survival molecules, Bcl-2, survivin and cyclinD1, and increased the cleavage of PARP, compared to RAD001 or cisplatin alone. Transfection of p53 into the Hep3B cell line increased the sensitivity of tumor cells to cisplatin. The suppression of HCC tumor growth in vivo was enhanced by RAD001 combined with cisplatin, accompanied by a significant increase in the number of apoptotic cells in tumor tissues. This study demonstrates that inhibition of mTOR suppresses tumor growth and sensitizes tumor cells to chemocytotoxic agents. © 2008 Elsevier Ireland Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/59161
ISSN
2015 Impact Factor: 5.992
2015 SCImago Journal Rankings: 2.331
ISI Accession Number ID
Funding AgencyGrant Number
Seed Funding Program for Basic Research 2006
Sun Chieh Yeh Research Foundation
Funding Information:

The study was supported by the Seed Funding Program for Basic Research 2006 and Sun Chieh Yeh Research Foundation for Hepatobiliary and Pancreatic Surgery of the University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorTam, KHen_HK
dc.contributor.authorYang, ZFen_HK
dc.contributor.authorLau, CKen_HK
dc.contributor.authorLam, CTen_HK
dc.contributor.authorPang, RWCen_HK
dc.contributor.authorPoon, RTPen_HK
dc.date.accessioned2010-05-31T03:44:03Z-
dc.date.available2010-05-31T03:44:03Z-
dc.date.issued2009en_HK
dc.identifier.citationCancer Letters, 2009, v. 273 n. 2, p. 201-209en_HK
dc.identifier.issn0304-3835en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59161-
dc.description.abstractThe present study investigated the effect of mammalian target of rapamycin (mTOR) inhibition on HCC cells in vitro and in vivo, either alone or in combination with cytotoxic agents. In vitro, HCC cell lines were exposed to RAD001, an mTOR inhibitor, either alone or in combination with cisplatin. Alone, RAD001 suppressed cell proliferation in all cell lines tested, but did not induce apoptosis. RAD001 in combination with cisplatin induced a significant increase in the number of apoptotic cells, downregulated the expression of pro-survival molecules, Bcl-2, survivin and cyclinD1, and increased the cleavage of PARP, compared to RAD001 or cisplatin alone. Transfection of p53 into the Hep3B cell line increased the sensitivity of tumor cells to cisplatin. The suppression of HCC tumor growth in vivo was enhanced by RAD001 combined with cisplatin, accompanied by a significant increase in the number of apoptotic cells in tumor tissues. This study demonstrates that inhibition of mTOR suppresses tumor growth and sensitizes tumor cells to chemocytotoxic agents. © 2008 Elsevier Ireland Ltd. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canleten_HK
dc.relation.ispartofCancer Lettersen_HK
dc.rightsCancer Letters. Copyright © Elsevier Ireland Ltd.en_HK
dc.subjectChemoresistanceen_HK
dc.subjectChemosensitivityen_HK
dc.subjectHCCen_HK
dc.subjectmTORen_HK
dc.subjectp53en_HK
dc.subjectRAD001en_HK
dc.titleInhibition of mTOR enhances chemosensitivity in hepatocellular carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0304-3835&volume=273&issue=2&spage=201&epage=209&date=2009&atitle=Inhibition+of+mTOR+enhances+chemosensitivity+in+hepatocellular+carcinomaen_HK
dc.identifier.emailPang, RWC: robertap@hkucc.hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_HK
dc.identifier.authorityPang, RWC=rp00274en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.canlet.2008.08.018en_HK
dc.identifier.pmid18824293-
dc.identifier.scopuseid_2-s2.0-57349106607en_HK
dc.identifier.hkuros154431en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-57349106607&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume273en_HK
dc.identifier.issue2en_HK
dc.identifier.spage201en_HK
dc.identifier.epage209en_HK
dc.identifier.isiWOS:000262582100003-
dc.publisher.placeIrelanden_HK
dc.identifier.scopusauthoridTam, KH=7201692833en_HK
dc.identifier.scopusauthoridYang, ZF=39863860200en_HK
dc.identifier.scopusauthoridLau, CK=7401968442en_HK
dc.identifier.scopusauthoridLam, CT=7402989860en_HK
dc.identifier.scopusauthoridPang, RWC=7004376659en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK

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