File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Adenovirus-mediated down-regulation of X-linked inhibitor of apoptosis protein inhibits colon cancer

TitleAdenovirus-mediated down-regulation of X-linked inhibitor of apoptosis protein inhibits colon cancer
Authors
Issue Date2009
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://mct.aacrjournals.org/
Citation
Molecular Cancer Therapeutics, 2009, v. 8 n. 9, p. 2762-2770 How to Cite?
AbstractOur previous studies and those of others have indicated that X-linked inhibitor of apoptosis protein (XIAP) holds promise as a target gene in colon cancer gene therapy. In this study, we constructed an adenoviral vector to deliver small hairpin RNA (shRNA) against XIAP (XIAP-shRNA) into colon cancer cells and tested its therapeutic efficacy in vitro and in vivo. We first confirmed an overexpression of XIAP in colon cancer cells and human cancer tissues. We then designed XIAP-small interfering RNA (siRNA) and confirmed the knockdown effect of these siRNAs in colon cancer cells. The sequences of the effective siRNAs were converted into shRNA and then packed into replication-deficient adenoviral vectors using BLOCK-iT Adenoviral RNAi Expression System to generate Adv-XIAP-shRNA. Infection of HT29 and HCT116 cells with Adv-XIAP-shRNA led to enhanced caspase-3 activity, which was associated with increased apoptosis and reduced cell proliferation. The therapeutic effect of Adv-XIAP-shRNA was then tested in xenograft tumors in nude mice.We showed that treatment of the xenograft tumors derived from HCT116 cells with Adv-XIAP-shRNA resulted in a retardation of tumor growth, which was associated with enhanced apoptosis, increased caspase-3 activity, and reduced expression of proliferating cell nuclear antigen in the tumor tissues. Treatment of xenograft tumors with Adv-XIAP-shRNA did not affect the expressions of inflammatory cytokines in tumor-bearing mice. Thus, Adv-XIAP-shRNA-mediated down-regulation of XIAP exerts a therapeutic effect in colon cancer by promoting apoptosis and inhibiting proliferation of colon cancer cells, and the antitumor effect of Adv-XIAP-shRNA was unlikely to be related to virus-induced immune response. Copyright © 2009 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/129015
ISSN
2015 Impact Factor: 5.579
2015 SCImago Journal Rankings: 3.224
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorDai, Yen_HK
dc.contributor.authorQiao, Len_HK
dc.contributor.authorKwok, WCen_HK
dc.contributor.authorYang, Men_HK
dc.contributor.authorYe, Jen_HK
dc.contributor.authorZhang, Ren_HK
dc.contributor.authorMa, Jen_HK
dc.contributor.authorZou, Ben_HK
dc.contributor.authorLam, CSCen_HK
dc.contributor.authorWang, Jen_HK
dc.contributor.authorPang, Ren_HK
dc.contributor.authorTan, VPYen_HK
dc.contributor.authorLan, HYen_HK
dc.contributor.authorWong, BCYen_HK
dc.date.accessioned2010-12-17T03:56:32Z-
dc.date.available2010-12-17T03:56:32Z-
dc.date.issued2009en_HK
dc.identifier.citationMolecular Cancer Therapeutics, 2009, v. 8 n. 9, p. 2762-2770en_HK
dc.identifier.issn1535-7163en_HK
dc.identifier.urihttp://hdl.handle.net/10722/129015-
dc.description.abstractOur previous studies and those of others have indicated that X-linked inhibitor of apoptosis protein (XIAP) holds promise as a target gene in colon cancer gene therapy. In this study, we constructed an adenoviral vector to deliver small hairpin RNA (shRNA) against XIAP (XIAP-shRNA) into colon cancer cells and tested its therapeutic efficacy in vitro and in vivo. We first confirmed an overexpression of XIAP in colon cancer cells and human cancer tissues. We then designed XIAP-small interfering RNA (siRNA) and confirmed the knockdown effect of these siRNAs in colon cancer cells. The sequences of the effective siRNAs were converted into shRNA and then packed into replication-deficient adenoviral vectors using BLOCK-iT Adenoviral RNAi Expression System to generate Adv-XIAP-shRNA. Infection of HT29 and HCT116 cells with Adv-XIAP-shRNA led to enhanced caspase-3 activity, which was associated with increased apoptosis and reduced cell proliferation. The therapeutic effect of Adv-XIAP-shRNA was then tested in xenograft tumors in nude mice.We showed that treatment of the xenograft tumors derived from HCT116 cells with Adv-XIAP-shRNA resulted in a retardation of tumor growth, which was associated with enhanced apoptosis, increased caspase-3 activity, and reduced expression of proliferating cell nuclear antigen in the tumor tissues. Treatment of xenograft tumors with Adv-XIAP-shRNA did not affect the expressions of inflammatory cytokines in tumor-bearing mice. Thus, Adv-XIAP-shRNA-mediated down-regulation of XIAP exerts a therapeutic effect in colon cancer by promoting apoptosis and inhibiting proliferation of colon cancer cells, and the antitumor effect of Adv-XIAP-shRNA was unlikely to be related to virus-induced immune response. Copyright © 2009 American Association for Cancer Research.en_HK
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://mct.aacrjournals.org/en_HK
dc.relation.ispartofMolecular Cancer Therapeuticsen_HK
dc.subject.meshAdenoviridae - physiology-
dc.subject.meshAnimals-
dc.subject.meshColonic Neoplasms - prevention and control-
dc.subject.meshDown-Regulation-
dc.subject.meshX-Linked Inhibitor of Apoptosis Protein - genetics - physiology-
dc.titleAdenovirus-mediated down-regulation of X-linked inhibitor of apoptosis protein inhibits colon canceren_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1535-7163&volume=8&issue=9&spage=2762&epage=2770&date=2009&atitle=Adenovirus-mediated+down-regulation+of+X-linked+inhibitor+of+apoptosis+protein+inhibits+colon+cancer-
dc.identifier.emailQiao, L: lq8688@hotmail.comen_HK
dc.identifier.emailWang, J: jidewang@gmail.comen_HK
dc.identifier.emailPang, R: robertap@hku.hken_HK
dc.identifier.emailTan, VPY: vpytan@hku.hken_HK
dc.identifier.emailWong, BCY: bcywong@hku.hken_HK
dc.identifier.authorityQiao, L=rp00513en_HK
dc.identifier.authorityWang, J=rp00491en_HK
dc.identifier.authorityPang, R=rp00274en_HK
dc.identifier.authorityTan, VPY=rp01458en_HK
dc.identifier.authorityWong, BCY=rp00429en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/1535-7163.MCT-09-0509en_HK
dc.identifier.pmid19737940-
dc.identifier.scopuseid_2-s2.0-70349495862en_HK
dc.identifier.hkuros170371-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-70349495862&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume8en_HK
dc.identifier.issue9en_HK
dc.identifier.spage2762en_HK
dc.identifier.epage2770en_HK
dc.identifier.isiWOS:000269968900029-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridDai, Y=7401512993en_HK
dc.identifier.scopusauthoridQiao, L=7202151719en_HK
dc.identifier.scopusauthoridKwok, WC=24171150800en_HK
dc.identifier.scopusauthoridYang, M=7404927250en_HK
dc.identifier.scopusauthoridYe, J=23669624100en_HK
dc.identifier.scopusauthoridZhang, R=9842860900en_HK
dc.identifier.scopusauthoridMa, J=35275386200en_HK
dc.identifier.scopusauthoridZou, B=35228257300en_HK
dc.identifier.scopusauthoridLam, CSC=35332626500en_HK
dc.identifier.scopusauthoridWang, J=35309087500en_HK
dc.identifier.scopusauthoridPang, R=7004376659en_HK
dc.identifier.scopusauthoridTan, VPY=24449627600en_HK
dc.identifier.scopusauthoridLan, HY=24544799000en_HK
dc.identifier.scopusauthoridWong, BCY=7402023340en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats