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Article: FTY720, a fungus metabolite, inhibits in vivo growth of androgen-independent prostate cancer

TitleFTY720, a fungus metabolite, inhibits in vivo growth of androgen-independent prostate cancer
Authors
KeywordsAngiogenesis
Apoptosis
FTY720
Proliferation
Prostate cancer
Issue Date2005
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, 2005, v. 117 n. 6, p. 1039-1048 How to Cite?
AbstractFTY720, a derivative of fungus, has demonstrated dramatic anticancer effect in several malignancies recently. Our study evaluates the therapeutic potential of FTY720 in the treatment of androgen-independent prostate cancer using a human prostate cancer xenograft in nude mice. CWR22R, an androgen-independent human prostate tumor xenograft was inoculated into castrated nude mice and the animals were administrated with either normal saline or FTY720 (10 mg/kg) through intraperitoneal (i.p.) injection for 20 days. Body weight and tumor volume were recorded every 2 days, and serum prostate specific antigen (PSA) levels were also measured before and after the treatment. The effect of FTY720 on tumor cell proliferation was examined using antibodies against PCNA and Ki-67 by immunohistochemical staining, MTT assay and colony forming assay, whereas apoptotic effect of FTY720 was evaluated by TUNEL assay and immunostaining using antibodies against cleaved caspase 3 and Bcl-2. In addition, the potential inhibitory effect of FTY720 on prostate cancer angiogenesis and metastasis was investigated by immunostaining of CD31, VEGF, E-cadherin and β-catenin. Our results showed that FTY720 treatment led to suppression of CWR22R tumor growth without causing any detectable side effects in nude mice. The FTY720-induced tumor suppression was correlated with decreased serum PSA level as well as reduced proliferation rate, suppression of angiogenic factors, and restoration of E-cadherin and β-catenin expression. In addition, the FTY720-treated tumors showed increased apoptosis rate demonstrated by increased TUNEL- and cleaved caspase 3-positive cells, and decreased Bcl-2 expression. Our results suggest a potential novel agent in the suppression of androgen-independent prostate cancer. © 2005 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/67874
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.657
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChua, CWen_HK
dc.contributor.authorLee, DTWen_HK
dc.contributor.authorLing, MTen_HK
dc.contributor.authorZhou, Cen_HK
dc.contributor.authorMan, Ken_HK
dc.contributor.authorHo, Jen_HK
dc.contributor.authorChan, FLen_HK
dc.contributor.authorWang, Xen_HK
dc.contributor.authorWong, YCen_HK
dc.date.accessioned2010-09-06T05:59:03Z-
dc.date.available2010-09-06T05:59:03Z-
dc.date.issued2005en_HK
dc.identifier.citationInternational Journal Of Cancer, 2005, v. 117 n. 6, p. 1039-1048en_HK
dc.identifier.issn0020-7136en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67874-
dc.description.abstractFTY720, a derivative of fungus, has demonstrated dramatic anticancer effect in several malignancies recently. Our study evaluates the therapeutic potential of FTY720 in the treatment of androgen-independent prostate cancer using a human prostate cancer xenograft in nude mice. CWR22R, an androgen-independent human prostate tumor xenograft was inoculated into castrated nude mice and the animals were administrated with either normal saline or FTY720 (10 mg/kg) through intraperitoneal (i.p.) injection for 20 days. Body weight and tumor volume were recorded every 2 days, and serum prostate specific antigen (PSA) levels were also measured before and after the treatment. The effect of FTY720 on tumor cell proliferation was examined using antibodies against PCNA and Ki-67 by immunohistochemical staining, MTT assay and colony forming assay, whereas apoptotic effect of FTY720 was evaluated by TUNEL assay and immunostaining using antibodies against cleaved caspase 3 and Bcl-2. In addition, the potential inhibitory effect of FTY720 on prostate cancer angiogenesis and metastasis was investigated by immunostaining of CD31, VEGF, E-cadherin and β-catenin. Our results showed that FTY720 treatment led to suppression of CWR22R tumor growth without causing any detectable side effects in nude mice. The FTY720-induced tumor suppression was correlated with decreased serum PSA level as well as reduced proliferation rate, suppression of angiogenic factors, and restoration of E-cadherin and β-catenin expression. In addition, the FTY720-treated tumors showed increased apoptosis rate demonstrated by increased TUNEL- and cleaved caspase 3-positive cells, and decreased Bcl-2 expression. Our results suggest a potential novel agent in the suppression of androgen-independent prostate cancer. © 2005 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.subjectAngiogenesisen_HK
dc.subjectApoptosisen_HK
dc.subjectFTY720en_HK
dc.subjectProliferationen_HK
dc.subjectProstate canceren_HK
dc.subject.meshAndrogens - pharmacologyen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAntigens, CD31 - analysisen_HK
dc.subject.meshApoptosis - drug effectsen_HK
dc.subject.meshBody Weighten_HK
dc.subject.meshCadherins - analysisen_HK
dc.subject.meshCaspase 3en_HK
dc.subject.meshCaspases - analysisen_HK
dc.subject.meshCell Division - drug effectsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshImmunohistochemistryen_HK
dc.subject.meshIn Situ Nick-End Labelingen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Nudeen_HK
dc.subject.meshNeoplasm Metastasis - prevention & controlen_HK
dc.subject.meshNeoplasm Transplantationen_HK
dc.subject.meshNeovascularization, Pathologic - prevention & controlen_HK
dc.subject.meshOrchiectomyen_HK
dc.subject.meshPropylene Glycols - administration & dosage - toxicityen_HK
dc.subject.meshProstate-Specific Antigen - blooden_HK
dc.subject.meshProstatic Neoplasms - chemistry - drug therapy - pathologyen_HK
dc.subject.meshProto-Oncogene Proteins c-bcl-2 - analysisen_HK
dc.subject.meshSphingosine - analogs & derivativesen_HK
dc.subject.meshVascular Endothelial Growth Factor A - analysisen_HK
dc.subject.meshbeta Catenin - analysisen_HK
dc.titleFTY720, a fungus metabolite, inhibits in vivo growth of androgen-independent prostate canceren_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0020-7136&volume=117&spage=1039&epage=1048&date=2005&atitle=FTY720,+a+fungus+metabolite,+inhibits+in+vivo+growth+of+androgen-independent+prostate+canceren_HK
dc.identifier.emailLing, MT: patling@hkucc.hku.hken_HK
dc.identifier.emailMan, K: kwanman@hkucc.hku.hken_HK
dc.identifier.emailWong, YC: ycwong@hkucc.hku.hken_HK
dc.identifier.authorityLing, MT=rp00449en_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/ijc.21243en_HK
dc.identifier.pmid15986440en_HK
dc.identifier.scopuseid_2-s2.0-28044460091en_HK
dc.identifier.hkuros115037en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-28044460091&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume117en_HK
dc.identifier.issue6en_HK
dc.identifier.spage1039en_HK
dc.identifier.epage1048en_HK
dc.identifier.isiWOS:000233384900022-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChua, CW=9437494600en_HK
dc.identifier.scopusauthoridLee, DTW=7406666118en_HK
dc.identifier.scopusauthoridLing, MT=7102229780en_HK
dc.identifier.scopusauthoridZhou, C=55245030500en_HK
dc.identifier.scopusauthoridMan, K=7101754072en_HK
dc.identifier.scopusauthoridHo, J=55166750600en_HK
dc.identifier.scopusauthoridChan, FL=7202586505en_HK
dc.identifier.scopusauthoridWang, X=7501854829en_HK
dc.identifier.scopusauthoridWong, YC=7403041798en_HK

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