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Article: Restoration of XAF1 expression induces apoptosis and inhibits tumor growth in gastric cancer

TitleRestoration of XAF1 expression induces apoptosis and inhibits tumor growth in gastric cancer
Authors
KeywordsAdenovirus
Apoptosis
Cell cycle arrest
Gastric cancer
Gene therapy
TRAIL
Tumorigenesis
XAF1
Issue Date2009
PublisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
Citation
International Journal Of Cancer, 2009, v. 125 n. 3, p. 688-697 How to Cite?
AbstractXAF1 (XIAP-associated factor 1) is a novel XIAP binding protein that can antagonize XIAP and sensitize cells to other cell death triggers. Our previous results have shown that aberrant hypermethylation of the CpG sites in XAF1 promoter is strongly associated with lower expression of XAF1 in gastric cancers. In our study, we investigated the effect of restoration of XAF1 expression on growth of gastric cancers. We found that the restoration of XAF1 expression suppressed anchorage-dependent and -independent growth and increased sensitivity to TRAIL and druginduced apoptosis. Stable cell clones expressing XAF1 exhibited delayed tumor initiation in nude mice. Restoration of XAF1 expression mediated by adenovirus vector greatly increased apoptosis in gastric cancer cell lines in a time- and dose-dependent manner and sensitized cancer cells to TRAIL and drugs-induced apoptosis. Adeno-XAF1 transduction induced cell cycle G2/M arrest and upregulated the expression of p21 and downregulated the expression of cyclin B1 and cdc2. Notably, adeno-XAF1 treatment significantly inhibited tumor growth, strongly enhanced the antitumor activity of TRAIL in a gastric cancer xenograft model in vivo, and significantly prolonged the survival time of animals bearing tumor xenografts. Complete eradication of established tumors was achieved on combined treatment with adeno-XAF1 and TRAIL. Our results document that the restoration of XAF1 inhibits gastric tumorigenesis and tumor growth and that XAF1 is a promising candidate for cancer gene therapy. © 2009 UICC.
Persistent Identifierhttp://hdl.handle.net/10722/163259
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.657
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council of Hong Kong Special Administrative RegionHKU 7482/03M
Gastroenterological Research Fund of University of Hong Kong
University Department of Medicine
Canadian Institutes of Health Research
National Cancer Institute of Canada
National Natural Science Foundation of China30572142
Funding Information:

Grant sponsor: Research Grant Council of Hong Kong Special Administrative Region; Grant number: HKU 7482/03M. Grant sponsors: Gastroenterological Research Fund of University of Hong Kong, University Department of Medicine, Canadian Institutes of Health Research, National Cancer Institute of Canada; Grant sponsor: National Natural Science Foundation of China; Grant number: 30572142.

References

 

DC FieldValueLanguage
dc.contributor.authorShui, PTen_US
dc.contributor.authorListon, Pen_US
dc.contributor.authorJian, TCen_US
dc.contributor.authorLin, MCMen_US
dc.contributor.authorXiao, HJen_US
dc.contributor.authorYang, Yen_US
dc.contributor.authorGu, Qen_US
dc.contributor.authorShi, HJen_US
dc.contributor.authorChing, TLen_US
dc.contributor.authorHsiang, FKen_US
dc.contributor.authorKorneluk, RGen_US
dc.contributor.authorWong, BCYen_US
dc.date.accessioned2012-09-05T05:29:16Z-
dc.date.available2012-09-05T05:29:16Z-
dc.date.issued2009en_US
dc.identifier.citationInternational Journal Of Cancer, 2009, v. 125 n. 3, p. 688-697en_US
dc.identifier.issn0020-7136en_US
dc.identifier.urihttp://hdl.handle.net/10722/163259-
dc.description.abstractXAF1 (XIAP-associated factor 1) is a novel XIAP binding protein that can antagonize XIAP and sensitize cells to other cell death triggers. Our previous results have shown that aberrant hypermethylation of the CpG sites in XAF1 promoter is strongly associated with lower expression of XAF1 in gastric cancers. In our study, we investigated the effect of restoration of XAF1 expression on growth of gastric cancers. We found that the restoration of XAF1 expression suppressed anchorage-dependent and -independent growth and increased sensitivity to TRAIL and druginduced apoptosis. Stable cell clones expressing XAF1 exhibited delayed tumor initiation in nude mice. Restoration of XAF1 expression mediated by adenovirus vector greatly increased apoptosis in gastric cancer cell lines in a time- and dose-dependent manner and sensitized cancer cells to TRAIL and drugs-induced apoptosis. Adeno-XAF1 transduction induced cell cycle G2/M arrest and upregulated the expression of p21 and downregulated the expression of cyclin B1 and cdc2. Notably, adeno-XAF1 treatment significantly inhibited tumor growth, strongly enhanced the antitumor activity of TRAIL in a gastric cancer xenograft model in vivo, and significantly prolonged the survival time of animals bearing tumor xenografts. Complete eradication of established tumors was achieved on combined treatment with adeno-XAF1 and TRAIL. Our results document that the restoration of XAF1 inhibits gastric tumorigenesis and tumor growth and that XAF1 is a promising candidate for cancer gene therapy. © 2009 UICC.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/homeen_US
dc.relation.ispartofInternational Journal of Canceren_US
dc.rightsInternational Journal of Cancer. Copyright © John Wiley & Sons, Inc.-
dc.subjectAdenovirus-
dc.subjectApoptosis-
dc.subjectCell cycle arrest-
dc.subjectGastric cancer-
dc.subjectGene therapy-
dc.subjectTRAIL-
dc.subjectTumorigenesis-
dc.subjectXAF1-
dc.subject.meshAdenoviridaeen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols - Pharmacologyen_US
dc.subject.meshApoptosisen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCell Cycle - Geneticsen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCyclin B - Metabolismen_US
dc.subject.meshCyclin B1en_US
dc.subject.meshCyclin-Dependent Kinase Inhibitor P21 - Metabolismen_US
dc.subject.meshDisease Models, Animalen_US
dc.subject.meshDisease Progressionen_US
dc.subject.meshDown-Regulationen_US
dc.subject.meshDrug Synergismen_US
dc.subject.meshGene Expression Regulation, Neoplasticen_US
dc.subject.meshGene Therapy - Methodsen_US
dc.subject.meshGenetic Vectorsen_US
dc.subject.meshHumansen_US
dc.subject.meshIn Situ Nick-End Labelingen_US
dc.subject.meshIntracellular Signaling Peptides And Proteinsen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred Balb Cen_US
dc.subject.meshNeoplasm Proteins - Metabolism - Pharmacology - Therapeutic Useen_US
dc.subject.meshPlasmidsen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshStomach Neoplasms - Genetics - Metabolism - Pathology - Physiopathology - Therapyen_US
dc.subject.meshTnf-Related Apoptosis-Inducing Ligand - Metabolism - Pharmacologyen_US
dc.subject.meshTime Factorsen_US
dc.subject.meshTransduction, Geneticen_US
dc.subject.meshTransfectionen_US
dc.subject.meshTransplantation, Heterologousen_US
dc.subject.meshUp-Regulationen_US
dc.titleRestoration of XAF1 expression induces apoptosis and inhibits tumor growth in gastric canceren_US
dc.typeArticleen_US
dc.identifier.emailLin, MCM:mcllin@hkucc.hku.hken_US
dc.identifier.emailChing, TL:ctlum@graduate.hku.hken_US
dc.identifier.emailWong, BCY:bcywong@hku.hken_US
dc.identifier.authorityLin, MCM=rp00746en_US
dc.identifier.authorityChing, TL=rp00757en_US
dc.identifier.authorityWong, BCY=rp00429en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1002/ijc.24282en_US
dc.identifier.pmid19358264-
dc.identifier.scopuseid_2-s2.0-67650085249en_US
dc.identifier.hkuros155118-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67650085249&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume125en_US
dc.identifier.issue3en_US
dc.identifier.spage688en_US
dc.identifier.epage697en_US
dc.identifier.isiWOS:000267637600022-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridShui, PT=36123962600en_US
dc.identifier.scopusauthoridListon, P=7003752131en_US
dc.identifier.scopusauthoridJian, TC=26867735900en_US
dc.identifier.scopusauthoridLin, MCM=7404816359en_US
dc.identifier.scopusauthoridXiao, HJ=36124131400en_US
dc.identifier.scopusauthoridYang, Y=8675011000en_US
dc.identifier.scopusauthoridGu, Q=24469982400en_US
dc.identifier.scopusauthoridShi, HJ=36123933200en_US
dc.identifier.scopusauthoridChing, TL=7006889374en_US
dc.identifier.scopusauthoridHsiang, FK=16306692200en_US
dc.identifier.scopusauthoridKorneluk, RG=7004442003en_US
dc.identifier.scopusauthoridWong, BCY=7402023340en_US

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