A tankyrase inhibitor impairs tumor growth and angiogenesis through the Wnt/β-catenin attenuation

Autores
Bocchicchio, Sebastian; Marta Tesone; Irusta, Griselda
Año de publicación
2017
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Aberrant regulation of Wnt signaling pathway is a prevalent theme in cancer biology. While it has been demonstrated to be involved in many types of tumours it has been poorly studied in ovarian cancer. We analyzed the effect of inhibiting Wnt/β-catenin in a xenograft model of human ovarian cancer. A human ovarian adenocarcinoma cell line (IGROV-1) was subcutaneously injected in 6-8 weeksold female nude mice. Once the tumour was palpable, we injected a tankyrase inhibitor, which attenuates Wnt/β-catenin signalling (XAV939: 2.5 and 5 mg/kg) every two days three times. Mice were euthanized 3 days after the last injection. The involvement of Wnt/β-catenin pathway in tumour growth, morphology and angiogenesis was evaluated. Our results showed a significant decrease in tumour size when mice were treated with XAV939, which strikingly, was higher at the 2.5 mg/kg dose than the 5 mg/kg dose (day 7: no treated animals vs. 2.5 mg/kg group, p<0.001; no treated animals vs. 5 mg/ kg group: p< 0.05). No significant differences were appreciated in mice weight between groups. There was also a significant decrease in β-Catenin and Cyclin D1 levels measured by western blot at both doses used. On the other hand, we observed a decrease in the endothelial cell area stained with CD31 marker. Additionally, we detected a decrease in the periendothelial cell area, measured using α-Smooth-muscle-actin, compared with tumours from animals with no treatment. In hematoxilin-eosin stained sections of tumours we distinguished that the morphology notably changed after treatment with XAV939. A tumour loss of integrity and accumulation of interstitial fluid was evident and dose dependent. In conclusion, we demonstrate a clear involvement of Wnt/β-catenin in ovarian tumour growth and we suggest and implication of this pathway in tumour angiogenesis.
Fil: Bocchicchio, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Marta Tesone. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Irusta, Griselda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; LXV Reunión Anual de la Sociedad Argentina de Inmunología; Reunión de la Sociedad Argentina de Andrología; XLVI Reunión Anual de la Sociedad Argentina de Biofísica; XIX Reunión Anual de la Sociedad Argentina de Biología; XLIX Reunión Anual de la Sociedad Argentina de Farmacología Experimental; Reunión Anual de la Sociedad Argentina de Fisiología; Reunión de la Sociedad Argentina de Hematología y XXIX Reunión Anual de la Sociedad Argentina de Protozoología
Buenos Aires
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Investigación Bioquímica y Biología Molecular
Sociedad Argentina de Inmunología
Sociedad Argentina de Andrología
Sociedad Argentina de Biofísica
Sociedad Argentina de Biología
Sociedad Argentina de Farmacología Experimental
Sociedad Argentina de Fisiología
Sociedad Argentina de Hematología
Sociedad Argentina de Protozoología
Materia
WNT SYSTEM
NOTCH
ANGIOGENESIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/241925
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/241925
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A tankyrase inhibitor impairs tumor growth and angiogenesis through the Wnt/β-catenin attenuationBocchicchio, SebastianMarta TesoneIrusta, GriseldaWNT SYSTEMNOTCHANGIOGENESIShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Aberrant regulation of Wnt signaling pathway is a prevalent theme in cancer biology. While it has been demonstrated to be involved in many types of tumours it has been poorly studied in ovarian cancer. We analyzed the effect of inhibiting Wnt/β-catenin in a xenograft model of human ovarian cancer. A human ovarian adenocarcinoma cell line (IGROV-1) was subcutaneously injected in 6-8 weeksold female nude mice. Once the tumour was palpable, we injected a tankyrase inhibitor, which attenuates Wnt/β-catenin signalling (XAV939: 2.5 and 5 mg/kg) every two days three times. Mice were euthanized 3 days after the last injection. The involvement of Wnt/β-catenin pathway in tumour growth, morphology and angiogenesis was evaluated. Our results showed a significant decrease in tumour size when mice were treated with XAV939, which strikingly, was higher at the 2.5 mg/kg dose than the 5 mg/kg dose (day 7: no treated animals vs. 2.5 mg/kg group, p<0.001; no treated animals vs. 5 mg/ kg group: p< 0.05). No significant differences were appreciated in mice weight between groups. There was also a significant decrease in β-Catenin and Cyclin D1 levels measured by western blot at both doses used. On the other hand, we observed a decrease in the endothelial cell area stained with CD31 marker. Additionally, we detected a decrease in the periendothelial cell area, measured using α-Smooth-muscle-actin, compared with tumours from animals with no treatment. In hematoxilin-eosin stained sections of tumours we distinguished that the morphology notably changed after treatment with XAV939. A tumour loss of integrity and accumulation of interstitial fluid was evident and dose dependent. In conclusion, we demonstrate a clear involvement of Wnt/β-catenin in ovarian tumour growth and we suggest and implication of this pathway in tumour angiogenesis.Fil: Bocchicchio, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Marta Tesone. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Irusta, Griselda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaLXII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; LXV Reunión Anual de la Sociedad Argentina de Inmunología; Reunión de la Sociedad Argentina de Andrología; XLVI Reunión Anual de la Sociedad Argentina de Biofísica; XIX Reunión Anual de la Sociedad Argentina de Biología; XLIX Reunión Anual de la Sociedad Argentina de Farmacología Experimental; Reunión Anual de la Sociedad Argentina de Fisiología; Reunión de la Sociedad Argentina de Hematología y XXIX Reunión Anual de la Sociedad Argentina de ProtozoologíaBuenos AiresArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de Investigación Bioquímica y Biología MolecularSociedad Argentina de InmunologíaSociedad Argentina de AndrologíaSociedad Argentina de BiofísicaSociedad Argentina de BiologíaSociedad Argentina de Farmacología ExperimentalSociedad Argentina de FisiologíaSociedad Argentina de HematologíaSociedad Argentina de ProtozoologíaFundación Revista Medicina2017info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/241925A tankyrase inhibitor impairs tumor growth and angiogenesis through the Wnt/β-catenin attenuation; LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; LXV Reunión Anual de la Sociedad Argentina de Inmunología; Reunión de la Sociedad Argentina de Andrología; XLVI Reunión Anual de la Sociedad Argentina de Biofísica; XIX Reunión Anual de la Sociedad Argentina de Biología; XLIX Reunión Anual de la Sociedad Argentina de Farmacología Experimental; Reunión Anual de la Sociedad Argentina de Fisiología; Reunión de la Sociedad Argentina de Hematología y XXIX Reunión Anual de la Sociedad Argentina de Protozoología; Buenos Aires; Argentina; 2017; 462-4620025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicinaNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:38:46Zoai:ri.conicet.gov.ar:11336/241925instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:38:46.689CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A tankyrase inhibitor impairs tumor growth and angiogenesis through the Wnt/β-catenin attenuation
title A tankyrase inhibitor impairs tumor growth and angiogenesis through the Wnt/β-catenin attenuation
spellingShingle A tankyrase inhibitor impairs tumor growth and angiogenesis through the Wnt/β-catenin attenuation
Bocchicchio, Sebastian
WNT SYSTEM
NOTCH
ANGIOGENESIS
title_short A tankyrase inhibitor impairs tumor growth and angiogenesis through the Wnt/β-catenin attenuation
title_full A tankyrase inhibitor impairs tumor growth and angiogenesis through the Wnt/β-catenin attenuation
title_fullStr A tankyrase inhibitor impairs tumor growth and angiogenesis through the Wnt/β-catenin attenuation
title_full_unstemmed A tankyrase inhibitor impairs tumor growth and angiogenesis through the Wnt/β-catenin attenuation
title_sort A tankyrase inhibitor impairs tumor growth and angiogenesis through the Wnt/β-catenin attenuation
dc.creator.none.fl_str_mv Bocchicchio, Sebastian
Marta Tesone
Irusta, Griselda
author Bocchicchio, Sebastian
author_facet Bocchicchio, Sebastian
Marta Tesone
Irusta, Griselda
author_role author
author2 Marta Tesone
Irusta, Griselda
author2_role author
author
dc.subject.none.fl_str_mv WNT SYSTEM
NOTCH
ANGIOGENESIS
topic WNT SYSTEM
NOTCH
ANGIOGENESIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Aberrant regulation of Wnt signaling pathway is a prevalent theme in cancer biology. While it has been demonstrated to be involved in many types of tumours it has been poorly studied in ovarian cancer. We analyzed the effect of inhibiting Wnt/β-catenin in a xenograft model of human ovarian cancer. A human ovarian adenocarcinoma cell line (IGROV-1) was subcutaneously injected in 6-8 weeksold female nude mice. Once the tumour was palpable, we injected a tankyrase inhibitor, which attenuates Wnt/β-catenin signalling (XAV939: 2.5 and 5 mg/kg) every two days three times. Mice were euthanized 3 days after the last injection. The involvement of Wnt/β-catenin pathway in tumour growth, morphology and angiogenesis was evaluated. Our results showed a significant decrease in tumour size when mice were treated with XAV939, which strikingly, was higher at the 2.5 mg/kg dose than the 5 mg/kg dose (day 7: no treated animals vs. 2.5 mg/kg group, p<0.001; no treated animals vs. 5 mg/ kg group: p< 0.05). No significant differences were appreciated in mice weight between groups. There was also a significant decrease in β-Catenin and Cyclin D1 levels measured by western blot at both doses used. On the other hand, we observed a decrease in the endothelial cell area stained with CD31 marker. Additionally, we detected a decrease in the periendothelial cell area, measured using α-Smooth-muscle-actin, compared with tumours from animals with no treatment. In hematoxilin-eosin stained sections of tumours we distinguished that the morphology notably changed after treatment with XAV939. A tumour loss of integrity and accumulation of interstitial fluid was evident and dose dependent. In conclusion, we demonstrate a clear involvement of Wnt/β-catenin in ovarian tumour growth and we suggest and implication of this pathway in tumour angiogenesis.
Fil: Bocchicchio, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Marta Tesone. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Irusta, Griselda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; LXV Reunión Anual de la Sociedad Argentina de Inmunología; Reunión de la Sociedad Argentina de Andrología; XLVI Reunión Anual de la Sociedad Argentina de Biofísica; XIX Reunión Anual de la Sociedad Argentina de Biología; XLIX Reunión Anual de la Sociedad Argentina de Farmacología Experimental; Reunión Anual de la Sociedad Argentina de Fisiología; Reunión de la Sociedad Argentina de Hematología y XXIX Reunión Anual de la Sociedad Argentina de Protozoología
Buenos Aires
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Investigación Bioquímica y Biología Molecular
Sociedad Argentina de Inmunología
Sociedad Argentina de Andrología
Sociedad Argentina de Biofísica
Sociedad Argentina de Biología
Sociedad Argentina de Farmacología Experimental
Sociedad Argentina de Fisiología
Sociedad Argentina de Hematología
Sociedad Argentina de Protozoología
description Aberrant regulation of Wnt signaling pathway is a prevalent theme in cancer biology. While it has been demonstrated to be involved in many types of tumours it has been poorly studied in ovarian cancer. We analyzed the effect of inhibiting Wnt/β-catenin in a xenograft model of human ovarian cancer. A human ovarian adenocarcinoma cell line (IGROV-1) was subcutaneously injected in 6-8 weeksold female nude mice. Once the tumour was palpable, we injected a tankyrase inhibitor, which attenuates Wnt/β-catenin signalling (XAV939: 2.5 and 5 mg/kg) every two days three times. Mice were euthanized 3 days after the last injection. The involvement of Wnt/β-catenin pathway in tumour growth, morphology and angiogenesis was evaluated. Our results showed a significant decrease in tumour size when mice were treated with XAV939, which strikingly, was higher at the 2.5 mg/kg dose than the 5 mg/kg dose (day 7: no treated animals vs. 2.5 mg/kg group, p<0.001; no treated animals vs. 5 mg/ kg group: p< 0.05). No significant differences were appreciated in mice weight between groups. There was also a significant decrease in β-Catenin and Cyclin D1 levels measured by western blot at both doses used. On the other hand, we observed a decrease in the endothelial cell area stained with CD31 marker. Additionally, we detected a decrease in the periendothelial cell area, measured using α-Smooth-muscle-actin, compared with tumours from animals with no treatment. In hematoxilin-eosin stained sections of tumours we distinguished that the morphology notably changed after treatment with XAV939. A tumour loss of integrity and accumulation of interstitial fluid was evident and dose dependent. In conclusion, we demonstrate a clear involvement of Wnt/β-catenin in ovarian tumour growth and we suggest and implication of this pathway in tumour angiogenesis.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/241925
A tankyrase inhibitor impairs tumor growth and angiogenesis through the Wnt/β-catenin attenuation; LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; LXV Reunión Anual de la Sociedad Argentina de Inmunología; Reunión de la Sociedad Argentina de Andrología; XLVI Reunión Anual de la Sociedad Argentina de Biofísica; XIX Reunión Anual de la Sociedad Argentina de Biología; XLIX Reunión Anual de la Sociedad Argentina de Farmacología Experimental; Reunión Anual de la Sociedad Argentina de Fisiología; Reunión de la Sociedad Argentina de Hematología y XXIX Reunión Anual de la Sociedad Argentina de Protozoología; Buenos Aires; Argentina; 2017; 462-462
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/241925
identifier_str_mv A tankyrase inhibitor impairs tumor growth and angiogenesis through the Wnt/β-catenin attenuation; LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; LXV Reunión Anual de la Sociedad Argentina de Inmunología; Reunión de la Sociedad Argentina de Andrología; XLVI Reunión Anual de la Sociedad Argentina de Biofísica; XIX Reunión Anual de la Sociedad Argentina de Biología; XLIX Reunión Anual de la Sociedad Argentina de Farmacología Experimental; Reunión Anual de la Sociedad Argentina de Fisiología; Reunión de la Sociedad Argentina de Hematología y XXIX Reunión Anual de la Sociedad Argentina de Protozoología; Buenos Aires; Argentina; 2017; 462-462
0025-7680
1669-9106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicina
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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