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Article: Loss of XIAP sensitizes rosiglitazone-induced growth inhibition of colon cancer in vivo

TitleLoss of XIAP sensitizes rosiglitazone-induced growth inhibition of colon cancer in vivo
Authors
KeywordsColon cancer
in vivo
PPARγ
Rosiglitazone
Therapy
Issue Date2008
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, 2008, v. 122 n. 12, p. 2858-2863 How to Cite?
AbstractLigands for peroxisome proliferator-activated receptor gamma (PPARγ) possess anticancer properties. However, the efficacy of PPARγ ligands varies in different cancers. In colon cancer, the role of PPARγ and its ligands is controversial. We recently showed that downregulation of X-linked inhibitor of apoptosis protein (XIAP) could sensitize colon cancer cells to troglitazone, and 15-deoxy-D12,14-prostaglandin J2 (15-PGJ2) induced cell killing. In our study, we aimed to examine whether rosiglitazone, another more clinically relevant PPARγ ligand, has any synergistic anticancer effect with XIAP downregulation in colon cancer. Human colon cancer cell lines HCT116-XIAP +/+ cells and HCT116-XIAP -/- cells were treated with various concentrations of rosiglitazone. The effects of rosiglitazone on cell proliferation, apoptosis and growth of xenograft colon cancers were studied. Rosiglitazone barely suppressed the growth and only very weakly induced apoptosis in HCT116 cells in vitro. Loss of XIAP did not sensitize HCT116 cells to rosiglitazone-induced growth inhibition or apoptosis. In vivo studies revealed that rosiglitazone strongly suppressed the growth of xenograft colon cancer, especially tumors derived from HCT116-XIAP -/- cells. The rosiglitazone-treated tumor had reduced expression of ki-67 and lowered mitotic rate. Downregulation of XIAP was associated with an impaired activation of PPARγ by its ligand. Rosiglitazone induced marked upregulation of PTEN in HCT116-XIAP -/- cells, as well as in xenograft tumors derived from HCT116-XIAP -/- cells. We concluded that rosiglitazone significantly suppresses the growth of xenograft colon cancer, and downregulation of XIAP sensitizes the xenograft tumors to rosiglitazone-induced tumor suppression in vivo via upregulation of PTEN. © 2008 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/76842
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.657
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorDai, Yen_HK
dc.contributor.authorQiao, Len_HK
dc.contributor.authorKwok, WCen_HK
dc.contributor.authorZou, Ben_HK
dc.contributor.authorMa, Jen_HK
dc.contributor.authorLan, HYen_HK
dc.contributor.authorGu, Qen_HK
dc.contributor.authorLi, Zen_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorWong, BLWen_HK
dc.contributor.authorWong, BCYen_HK
dc.date.accessioned2010-09-06T07:25:30Z-
dc.date.available2010-09-06T07:25:30Z-
dc.date.issued2008en_HK
dc.identifier.citationInternational Journal Of Cancer, 2008, v. 122 n. 12, p. 2858-2863en_HK
dc.identifier.issn0020-7136en_HK
dc.identifier.urihttp://hdl.handle.net/10722/76842-
dc.description.abstractLigands for peroxisome proliferator-activated receptor gamma (PPARγ) possess anticancer properties. However, the efficacy of PPARγ ligands varies in different cancers. In colon cancer, the role of PPARγ and its ligands is controversial. We recently showed that downregulation of X-linked inhibitor of apoptosis protein (XIAP) could sensitize colon cancer cells to troglitazone, and 15-deoxy-D12,14-prostaglandin J2 (15-PGJ2) induced cell killing. In our study, we aimed to examine whether rosiglitazone, another more clinically relevant PPARγ ligand, has any synergistic anticancer effect with XIAP downregulation in colon cancer. Human colon cancer cell lines HCT116-XIAP +/+ cells and HCT116-XIAP -/- cells were treated with various concentrations of rosiglitazone. The effects of rosiglitazone on cell proliferation, apoptosis and growth of xenograft colon cancers were studied. Rosiglitazone barely suppressed the growth and only very weakly induced apoptosis in HCT116 cells in vitro. Loss of XIAP did not sensitize HCT116 cells to rosiglitazone-induced growth inhibition or apoptosis. In vivo studies revealed that rosiglitazone strongly suppressed the growth of xenograft colon cancer, especially tumors derived from HCT116-XIAP -/- cells. The rosiglitazone-treated tumor had reduced expression of ki-67 and lowered mitotic rate. Downregulation of XIAP was associated with an impaired activation of PPARγ by its ligand. Rosiglitazone induced marked upregulation of PTEN in HCT116-XIAP -/- cells, as well as in xenograft tumors derived from HCT116-XIAP -/- cells. We concluded that rosiglitazone significantly suppresses the growth of xenograft colon cancer, and downregulation of XIAP sensitizes the xenograft tumors to rosiglitazone-induced tumor suppression in vivo via upregulation of PTEN. © 2008 Wiley-Liss, Inc.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/homeen_HK
dc.relation.ispartofInternational Journal of Canceren_HK
dc.rightsInternational Journal of Cancer. Copyright © John Wiley & Sons, Inc.en_HK
dc.subjectColon canceren_HK
dc.subjectin vivoen_HK
dc.subjectPPARγen_HK
dc.subjectRosiglitazoneen_HK
dc.subjectTherapyen_HK
dc.subject.meshAntineoplastic Agents - pharmacologyen_HK
dc.subject.meshApoptosis - drug effectsen_HK
dc.subject.meshCaspase 3 - metabolismen_HK
dc.subject.meshCell Division - drug effectsen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshColonic Neoplasms - pathologyen_HK
dc.subject.meshDown-Regulationen_HK
dc.subject.meshHumansen_HK
dc.subject.meshIn Situ Nick-End Labelingen_HK
dc.subject.meshPPAR gamma - antagonists & inhibitorsen_HK
dc.subject.meshThiazolidinediones - pharmacologyen_HK
dc.subject.meshX-Linked Inhibitor of Apoptosis Protein - metabolismen_HK
dc.titleLoss of XIAP sensitizes rosiglitazone-induced growth inhibition of colon cancer in vivoen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0020-7136&volume=122&spage=2858&epage=63&date=2008&atitle=Loss+of+XIAP+sensitizes+Rosiglitazone-induced+growth+inhibition+of+colon+cancer+in+vivoen_HK
dc.identifier.emailQiao, L: lq8688@hotmail.comen_HK
dc.identifier.emailWong, BCY: bcywong@hku.hken_HK
dc.identifier.authorityQiao, L=rp00513en_HK
dc.identifier.authorityWong, BCY=rp00429en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/ijc.23443en_HK
dc.identifier.pmid18351648-
dc.identifier.scopuseid_2-s2.0-43049093730en_HK
dc.identifier.hkuros141381en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-43049093730&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume122en_HK
dc.identifier.issue12en_HK
dc.identifier.spage2858en_HK
dc.identifier.epage2863en_HK
dc.identifier.isiWOS:000256713800027-
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.scopusauthoridZou, B=35228257300en_HK
dc.identifier.scopusauthoridMa, J=35275386200en_HK
dc.identifier.scopusauthoridLan, HY=7102710832en_HK
dc.identifier.scopusauthoridGu, Q=24469982400en_HK
dc.identifier.scopusauthoridLi, Z=24171072000en_HK
dc.identifier.scopusauthoridWang, Y=23062601200en_HK
dc.identifier.scopusauthoridWong, BLW=24171921500en_HK
dc.identifier.scopusauthoridWong, BCY=7402023340en_HK

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