A proangiognenic factor improves gamma-secretase inhibitor antitumoral effect in ovarian cancer xenografts

Autores
Pazos, M. C.; Sequeira, Gonzalo Ricardo; Tesone, Marta; Irusta, Griselda
Año de publicación
2015
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Notch and PDGF systems are involved in angiogenic process in physiological and pathological conditions. Here, we developed tumours in nude mice injecting an epithelial ovarian tumour cell line. SKOV3 cells (1.106 cells in 100 μl) were inoculated subcutaneously into one flank of 6-10 week-old female nude mice. When the tumours were palpable, the mice were divided in three groups that received 1. Control, 2. DAPT (5mg/kg gamma-secretasa inhibitor), and 3. DAPT+PDGFB (0,1mg/kg). The treatments were administered during four consecutive days (day 1-4). At day 8, the animals were sacrificed and we determined: a. mice and tumour weight, b. tumour area, c. pericyte area and d. phosphor-AKT and PCNA (cell proliferation marker). Mice weight did not change between treatments. Tumour weight significantly decreased when PDGFB was co-administered with DAPT compared to Control group, but no differences were found between Control and DAPT treatments. Tumour area decreased with DAPT but not statistically different respect to Control. Interestingly, the cotreatment completely abolished the tumour growth, being the difference highly significant on days 7 and 8 post treatment. Similarly, the periendothelial area increased with PDGFB and DAPT administration. PCNA levels were significantly decreased in DAPT+PDGF group, but phosphorylated AKT did not change between groups. We conclude that PDGFB improves the antitumoral effect of gamma secretasa inhibitor, in part, recruiting periendothelial cells, stabilizing tumour vasculture, and thus, allowing the inhibitor to better reach the tumour and exert its antiproliferative effect.
Fil: Pazos, M. C.. 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: Sequeira, Gonzalo Ricardo. 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: Tesone, Marta. 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
XVI Annual Meeting of the Argentine Society of Biology
Chascomús
Argentina
Sociedad Argentina de Biología
Materia
CANCER DE OVARIO
NOTCH
ANGIOGENESIS
PDGF
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:11336/241927
Acceder
id CONICETDig_dbe2a0bcdabb565e7a731fc4a977a837
oai_identifier_str oai:ri.conicet.gov.ar:11336/241927
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A proangiognenic factor improves gamma-secretase inhibitor antitumoral effect in ovarian cancer xenograftsPazos, M. C.Sequeira, Gonzalo RicardoTesone, MartaIrusta, GriseldaCANCER DE OVARIONOTCHANGIOGENESISPDGFhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Notch and PDGF systems are involved in angiogenic process in physiological and pathological conditions. Here, we developed tumours in nude mice injecting an epithelial ovarian tumour cell line. SKOV3 cells (1.106 cells in 100 μl) were inoculated subcutaneously into one flank of 6-10 week-old female nude mice. When the tumours were palpable, the mice were divided in three groups that received 1. Control, 2. DAPT (5mg/kg gamma-secretasa inhibitor), and 3. DAPT+PDGFB (0,1mg/kg). The treatments were administered during four consecutive days (day 1-4). At day 8, the animals were sacrificed and we determined: a. mice and tumour weight, b. tumour area, c. pericyte area and d. phosphor-AKT and PCNA (cell proliferation marker). Mice weight did not change between treatments. Tumour weight significantly decreased when PDGFB was co-administered with DAPT compared to Control group, but no differences were found between Control and DAPT treatments. Tumour area decreased with DAPT but not statistically different respect to Control. Interestingly, the cotreatment completely abolished the tumour growth, being the difference highly significant on days 7 and 8 post treatment. Similarly, the periendothelial area increased with PDGFB and DAPT administration. PCNA levels were significantly decreased in DAPT+PDGF group, but phosphorylated AKT did not change between groups. We conclude that PDGFB improves the antitumoral effect of gamma secretasa inhibitor, in part, recruiting periendothelial cells, stabilizing tumour vasculture, and thus, allowing the inhibitor to better reach the tumour and exert its antiproliferative effect.Fil: Pazos, M. C.. 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: Sequeira, Gonzalo Ricardo. 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: Tesone, Marta. 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; ArgentinaXVI Annual Meeting of the Argentine Society of BiologyChascomúsArgentinaSociedad Argentina de BiologíaTech Science Press2015info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/mswordapplication/pdfhttp://hdl.handle.net/11336/241927A proangiognenic factor improves gamma-secretase inhibitor antitumoral effect in ovarian cancer xenografts; XVI Annual Meeting of the Argentine Society of Biology; Chascomús; Argentina; 2014; 1-31667-5746CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.biologia.org.ar/jornadas/jornadas-anteriores/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:16:47Zoai:ri.conicet.gov.ar:11336/241927instacron: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:34982025-09-29 10:16:47.799CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A proangiognenic factor improves gamma-secretase inhibitor antitumoral effect in ovarian cancer xenografts
title A proangiognenic factor improves gamma-secretase inhibitor antitumoral effect in ovarian cancer xenografts
spellingShingle A proangiognenic factor improves gamma-secretase inhibitor antitumoral effect in ovarian cancer xenografts
Pazos, M. C.
CANCER DE OVARIO
NOTCH
ANGIOGENESIS
PDGF
title_short A proangiognenic factor improves gamma-secretase inhibitor antitumoral effect in ovarian cancer xenografts
title_full A proangiognenic factor improves gamma-secretase inhibitor antitumoral effect in ovarian cancer xenografts
title_fullStr A proangiognenic factor improves gamma-secretase inhibitor antitumoral effect in ovarian cancer xenografts
title_full_unstemmed A proangiognenic factor improves gamma-secretase inhibitor antitumoral effect in ovarian cancer xenografts
title_sort A proangiognenic factor improves gamma-secretase inhibitor antitumoral effect in ovarian cancer xenografts
dc.creator.none.fl_str_mv Pazos, M. C.
Sequeira, Gonzalo Ricardo
Tesone, Marta
Irusta, Griselda
author Pazos, M. C.
author_facet Pazos, M. C.
Sequeira, Gonzalo Ricardo
Tesone, Marta
Irusta, Griselda
author_role author
author2 Sequeira, Gonzalo Ricardo
Tesone, Marta
Irusta, Griselda
author2_role author
author
author
dc.subject.none.fl_str_mv CANCER DE OVARIO
NOTCH
ANGIOGENESIS
PDGF
topic CANCER DE OVARIO
NOTCH
ANGIOGENESIS
PDGF
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Notch and PDGF systems are involved in angiogenic process in physiological and pathological conditions. Here, we developed tumours in nude mice injecting an epithelial ovarian tumour cell line. SKOV3 cells (1.106 cells in 100 μl) were inoculated subcutaneously into one flank of 6-10 week-old female nude mice. When the tumours were palpable, the mice were divided in three groups that received 1. Control, 2. DAPT (5mg/kg gamma-secretasa inhibitor), and 3. DAPT+PDGFB (0,1mg/kg). The treatments were administered during four consecutive days (day 1-4). At day 8, the animals were sacrificed and we determined: a. mice and tumour weight, b. tumour area, c. pericyte area and d. phosphor-AKT and PCNA (cell proliferation marker). Mice weight did not change between treatments. Tumour weight significantly decreased when PDGFB was co-administered with DAPT compared to Control group, but no differences were found between Control and DAPT treatments. Tumour area decreased with DAPT but not statistically different respect to Control. Interestingly, the cotreatment completely abolished the tumour growth, being the difference highly significant on days 7 and 8 post treatment. Similarly, the periendothelial area increased with PDGFB and DAPT administration. PCNA levels were significantly decreased in DAPT+PDGF group, but phosphorylated AKT did not change between groups. We conclude that PDGFB improves the antitumoral effect of gamma secretasa inhibitor, in part, recruiting periendothelial cells, stabilizing tumour vasculture, and thus, allowing the inhibitor to better reach the tumour and exert its antiproliferative effect.
Fil: Pazos, M. C.. 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: Sequeira, Gonzalo Ricardo. 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: Tesone, Marta. 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
XVI Annual Meeting of the Argentine Society of Biology
Chascomús
Argentina
Sociedad Argentina de Biología
description Notch and PDGF systems are involved in angiogenic process in physiological and pathological conditions. Here, we developed tumours in nude mice injecting an epithelial ovarian tumour cell line. SKOV3 cells (1.106 cells in 100 μl) were inoculated subcutaneously into one flank of 6-10 week-old female nude mice. When the tumours were palpable, the mice were divided in three groups that received 1. Control, 2. DAPT (5mg/kg gamma-secretasa inhibitor), and 3. DAPT+PDGFB (0,1mg/kg). The treatments were administered during four consecutive days (day 1-4). At day 8, the animals were sacrificed and we determined: a. mice and tumour weight, b. tumour area, c. pericyte area and d. phosphor-AKT and PCNA (cell proliferation marker). Mice weight did not change between treatments. Tumour weight significantly decreased when PDGFB was co-administered with DAPT compared to Control group, but no differences were found between Control and DAPT treatments. Tumour area decreased with DAPT but not statistically different respect to Control. Interestingly, the cotreatment completely abolished the tumour growth, being the difference highly significant on days 7 and 8 post treatment. Similarly, the periendothelial area increased with PDGFB and DAPT administration. PCNA levels were significantly decreased in DAPT+PDGF group, but phosphorylated AKT did not change between groups. We conclude that PDGFB improves the antitumoral effect of gamma secretasa inhibitor, in part, recruiting periendothelial cells, stabilizing tumour vasculture, and thus, allowing the inhibitor to better reach the tumour and exert its antiproliferative effect.
publishDate 2015
dc.date.none.fl_str_mv 2015
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/11336/241927
A proangiognenic factor improves gamma-secretase inhibitor antitumoral effect in ovarian cancer xenografts; XVI Annual Meeting of the Argentine Society of Biology; Chascomús; Argentina; 2014; 1-3
1667-5746
CONICET Digital
CONICET
url http://hdl.handle.net/11336/241927
identifier_str_mv A proangiognenic factor improves gamma-secretase inhibitor antitumoral effect in ovarian cancer xenografts; XVI Annual Meeting of the Argentine Society of Biology; Chascomús; Argentina; 2014; 1-3
1667-5746
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.biologia.org.ar/jornadas/jornadas-anteriores/
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/
dc.format.none.fl_str_mv application/pdf
application/msword
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Tech Science Press
publisher.none.fl_str_mv Tech Science Press
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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score 13.070432

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