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Article: Gene therapy for colon cancer by adeno-associated viral vector-mediated transfer of survivin Cys84Ala mutant

TitleGene therapy for colon cancer by adeno-associated viral vector-mediated transfer of survivin Cys84Ala mutant
Authors
Issue Date2005
PublisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastro
Citation
Gastroenterology, 2005, v. 128 n. 2, p. 361-375 How to Cite?
AbstractBackground & Aims: Reactivation of survivin expression is involved in carcinogenesis and angiogenesis in colon cancer. Previous in vitro studies showed that mutation of the cysteine residue at position 84 (Cys84Ala) of survivin generates a dominant-negative mutant that triggers mitotic catastrophe and apoptosis. We investigated the therapeutic effect of the adeno-associated virus (AAV)-mediated survivin mutant (Cys84Ala) on colon cancer. Methods: Survivin mutant (Cys84Ala) (Sur-Mut(Cys84Ala)) was cloned into the AAV expression vector pAM/CAG-WPRE.poly(A) to generate recombinant AAV-Sur-Mut(Cys84Ala) virus. Cell proliferation, apoptosis, mitotic catastrophe, and tumor growth were measured in vitro and in vivo. Results: Transduction of colon cancer cells with rAAV-Sur-Mut(Cys84Ala) inhibited cell proliferation and induced apoptosis and mitotic catastrophe in vitro. rAAV-Sur-Mut(Cys84Ala) sensitized colon cancer cells to chemotherapeutic drugs. Furthermore, expression of survivin mutant mediated by AAV inhibited tumorigenesis in colon cancer cells. Intratumoral injection of rAAV-Sur-Mut(Cys84Ala) significantly induced apoptosis and mitotic catastrophe and inhibited angiogenesis and tumor growth in a colon cancer xenograft model in vivo. No obvious cytotoxicity to other tissues was observed. More importantly, rAAV-Sur-Mut(Cys84Ala) expression strongly enhanced the antitumor activity of 5-Fluorouracil (5-FU), resulting in regression of established tumors. Conclusions: Our results showed that rAAV-Sur-Mut(Cys84Ala) induced apoptosis and mitotic catastrophe and inhibited tumor angiogenesis and tumor growth. Thus, use of AAV-mediated survivin mutant (Cys84Ala) is a promising strategy in colon cancer gene therapy. © 2005 by the American Gastroenterological Association.
Persistent Identifierhttp://hdl.handle.net/10722/77014
ISSN
2015 Impact Factor: 18.187
2015 SCImago Journal Rankings: 7.170
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTu, SPen_HK
dc.contributor.authorCui, JTen_HK
dc.contributor.authorListon, Pen_HK
dc.contributor.authorHuajiang, Xen_HK
dc.contributor.authorXu, Ren_HK
dc.contributor.authorLin, MCMen_HK
dc.contributor.authorZhu, YBen_HK
dc.contributor.authorZou, Ben_HK
dc.contributor.authorNg, SSMen_HK
dc.contributor.authorJiang, SHen_HK
dc.contributor.authorXia, HHXen_HK
dc.contributor.authorWong, WMen_HK
dc.contributor.authorChan, AOOen_HK
dc.contributor.authorYuen, MFen_HK
dc.contributor.authorLam, SKen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorWong, BCYen_HK
dc.date.accessioned2010-09-06T07:27:20Z-
dc.date.available2010-09-06T07:27:20Z-
dc.date.issued2005en_HK
dc.identifier.citationGastroenterology, 2005, v. 128 n. 2, p. 361-375en_HK
dc.identifier.issn0016-5085en_HK
dc.identifier.urihttp://hdl.handle.net/10722/77014-
dc.description.abstractBackground & Aims: Reactivation of survivin expression is involved in carcinogenesis and angiogenesis in colon cancer. Previous in vitro studies showed that mutation of the cysteine residue at position 84 (Cys84Ala) of survivin generates a dominant-negative mutant that triggers mitotic catastrophe and apoptosis. We investigated the therapeutic effect of the adeno-associated virus (AAV)-mediated survivin mutant (Cys84Ala) on colon cancer. Methods: Survivin mutant (Cys84Ala) (Sur-Mut(Cys84Ala)) was cloned into the AAV expression vector pAM/CAG-WPRE.poly(A) to generate recombinant AAV-Sur-Mut(Cys84Ala) virus. Cell proliferation, apoptosis, mitotic catastrophe, and tumor growth were measured in vitro and in vivo. Results: Transduction of colon cancer cells with rAAV-Sur-Mut(Cys84Ala) inhibited cell proliferation and induced apoptosis and mitotic catastrophe in vitro. rAAV-Sur-Mut(Cys84Ala) sensitized colon cancer cells to chemotherapeutic drugs. Furthermore, expression of survivin mutant mediated by AAV inhibited tumorigenesis in colon cancer cells. Intratumoral injection of rAAV-Sur-Mut(Cys84Ala) significantly induced apoptosis and mitotic catastrophe and inhibited angiogenesis and tumor growth in a colon cancer xenograft model in vivo. No obvious cytotoxicity to other tissues was observed. More importantly, rAAV-Sur-Mut(Cys84Ala) expression strongly enhanced the antitumor activity of 5-Fluorouracil (5-FU), resulting in regression of established tumors. Conclusions: Our results showed that rAAV-Sur-Mut(Cys84Ala) induced apoptosis and mitotic catastrophe and inhibited tumor angiogenesis and tumor growth. Thus, use of AAV-mediated survivin mutant (Cys84Ala) is a promising strategy in colon cancer gene therapy. © 2005 by the American Gastroenterological Association.en_HK
dc.languageengen_HK
dc.publisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastroen_HK
dc.relation.ispartofGastroenterologyen_HK
dc.titleGene therapy for colon cancer by adeno-associated viral vector-mediated transfer of survivin Cys84Ala mutanten_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0016-5085&volume=128&spage=361&epage=375&date=2005&atitle=Gene+Therapy+for+Colon+Cancer+by+Adeno-Associated+Viral+Vector-Mediated+Transfer+of+Survivin+Cys84Ala+Mutanten_HK
dc.identifier.emailLin, MCM: mcllin@hkucc.hku.hken_HK
dc.identifier.emailNg, SSM: ssmng@hku.hken_HK
dc.identifier.emailYuen, MF: mfyuen@hku.hken_HK
dc.identifier.emailWong, BCY: bcywong@hku.hken_HK
dc.identifier.authorityLin, MCM=rp00746en_HK
dc.identifier.authorityNg, SSM=rp00767en_HK
dc.identifier.authorityYuen, MF=rp00479en_HK
dc.identifier.authorityWong, BCY=rp00429en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1053/j.gastro.2004.11.058en_HK
dc.identifier.scopuseid_2-s2.0-14944359615en_HK
dc.identifier.hkuros97357en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-14944359615&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume128en_HK
dc.identifier.issue2en_HK
dc.identifier.spage361en_HK
dc.identifier.epage375en_HK
dc.identifier.isiWOS:000226799800018-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridTu, SP=7202726555en_HK
dc.identifier.scopusauthoridCui, JT=7401811557en_HK
dc.identifier.scopusauthoridListon, P=7003752131en_HK
dc.identifier.scopusauthoridHuajiang, X=8285040900en_HK
dc.identifier.scopusauthoridXu, R=7402813857en_HK
dc.identifier.scopusauthoridLin, MCM=7404816359en_HK
dc.identifier.scopusauthoridZhu, YB=7406072866en_HK
dc.identifier.scopusauthoridZou, B=35228257300en_HK
dc.identifier.scopusauthoridNg, SSM=7403358718en_HK
dc.identifier.scopusauthoridJiang, SH=7404453122en_HK
dc.identifier.scopusauthoridXia, HHX=8757161400en_HK
dc.identifier.scopusauthoridWong, WM=7403972413en_HK
dc.identifier.scopusauthoridChan, AOO=7403167965en_HK
dc.identifier.scopusauthoridYuen, MF=7102031955en_HK
dc.identifier.scopusauthoridLam, SK=55424391900en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridWong, BCY=7402023340en_HK

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