BMP7 promotes cisplatin chemoresistance of cervical cancer cells through the PI3K/AKT signaling pathway

Autores
Birkenstok, Cintia Noelia; Carriere, Pedro Matias; Novoa Díaz, María Belén; Zwenger, Ariel; Gentili, Claudia Rosana; Calvo, Natalia Graciela
Año de publicación
2024
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Chemotherapy with cisplatin is one of the standard treatments for patients with advanced or recurrent cervical cancer (CC). However, chemoresistance can develop, compromising its efficacy in clinical practice. We previously observed an indirect role of bone morphogenetic protein 7 (BMP7) in cisplatin chemoresistance and in processes associated with cell plasticity in CC by acting on endothelial cells. In this work, the objective was to investigate a direct role of BMP7 in chemoresistance to cisplatin in CC and the molecular mechanisms involved. First, we evaluated the viability of both control HeLa cells and HeLa cells overexpressing BMP7, obtained via CRISPR/dCas9 technology, when exposed to different concentrations of cisplatin using the neutral red assay. Compared to control cells, BMP7-overexpressing HeLa cells exhibited higher viability under increasing concentrations of cisplatin and a higher half-maximal inhibitory concentration (IC50) of cisplatin. These results were confirmed by trypan blue dye exclusion testing. Then, we investigated the impact of this cytokine on markers involved in apoptosis and cell cycle regulation modulated by cisplatin using Western Blot analysis. We found that overexpression of BMP7 reverses the PARP cleavage, the decrease in cyclin D1 expression, and the Akt phosphorylation induced by cisplatin in CC cells. An increase in Akt phosphorylation levels was further observed in BMP7-overexpressing cells. Finally, we employed a trypan blue assay to determine the effect of LY294002, a phosphatidylinositol-3-kinase (PI3K) inhibitor, which is a key enzyme involved in the activation of Akt, on the cell viability of CC cells. LY294002 reversed the increase in cell viability induced by BMP7 under cisplatin treatment. Taken together, these results provide evidence that BMP7 plays a significant role in cisplatin resistance in cervical cancer cells by influencing the PI3K/Akt pathway.
Fil: Birkenstok, Cintia Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Carriere, Pedro Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Novoa Díaz, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Zwenger, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gentili, Claudia Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Calvo, Natalia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
LXIX Reunión Anual de la Sociedad Argentina de Investigación Clínica y XXVI Sociedad Argentina de Fisiología
Ciudad Autónoma de Buenos Aires
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Latinoamericana de Ciencias Fisiológicas
Sociedad Argentina de Fisiología
Materia
BMP7
CISPLATIN
CHEMORESISTANCE
CERVICAL CANCER
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:11336/264230
Acceder
id CONICETDig_48e9e9148670eb79c1acb7bbd55c8b2a
oai_identifier_str oai:ri.conicet.gov.ar:11336/264230
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling BMP7 promotes cisplatin chemoresistance of cervical cancer cells through the PI3K/AKT signaling pathwayBirkenstok, Cintia NoeliaCarriere, Pedro MatiasNovoa Díaz, María BelénZwenger, ArielGentili, Claudia RosanaCalvo, Natalia GracielaBMP7CISPLATINCHEMORESISTANCECERVICAL CANCERhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Chemotherapy with cisplatin is one of the standard treatments for patients with advanced or recurrent cervical cancer (CC). However, chemoresistance can develop, compromising its efficacy in clinical practice. We previously observed an indirect role of bone morphogenetic protein 7 (BMP7) in cisplatin chemoresistance and in processes associated with cell plasticity in CC by acting on endothelial cells. In this work, the objective was to investigate a direct role of BMP7 in chemoresistance to cisplatin in CC and the molecular mechanisms involved. First, we evaluated the viability of both control HeLa cells and HeLa cells overexpressing BMP7, obtained via CRISPR/dCas9 technology, when exposed to different concentrations of cisplatin using the neutral red assay. Compared to control cells, BMP7-overexpressing HeLa cells exhibited higher viability under increasing concentrations of cisplatin and a higher half-maximal inhibitory concentration (IC50) of cisplatin. These results were confirmed by trypan blue dye exclusion testing. Then, we investigated the impact of this cytokine on markers involved in apoptosis and cell cycle regulation modulated by cisplatin using Western Blot analysis. We found that overexpression of BMP7 reverses the PARP cleavage, the decrease in cyclin D1 expression, and the Akt phosphorylation induced by cisplatin in CC cells. An increase in Akt phosphorylation levels was further observed in BMP7-overexpressing cells. Finally, we employed a trypan blue assay to determine the effect of LY294002, a phosphatidylinositol-3-kinase (PI3K) inhibitor, which is a key enzyme involved in the activation of Akt, on the cell viability of CC cells. LY294002 reversed the increase in cell viability induced by BMP7 under cisplatin treatment. Taken together, these results provide evidence that BMP7 plays a significant role in cisplatin resistance in cervical cancer cells by influencing the PI3K/Akt pathway.Fil: Birkenstok, Cintia Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Carriere, Pedro Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Novoa Díaz, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Zwenger, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gentili, Claudia Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Calvo, Natalia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaLXIX Reunión Anual de la Sociedad Argentina de Investigación Clínica y XXVI Sociedad Argentina de FisiologíaCiudad Autónoma de Buenos AiresArgentinaSociedad Argentina de Investigación ClínicaAsociación Latinoamericana de Ciencias FisiológicasSociedad Argentina de FisiologíaFundación Revista Medicina2024info: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/11336/264230BMP7 promotes cisplatin chemoresistance of cervical cancer cells through the PI3K/AKT signaling pathway; LXIX Reunión Anual de la Sociedad Argentina de Investigación Clínica y XXVI Sociedad Argentina de Fisiología; Ciudad Autónoma de Buenos Aires; Argentina; 2024; 173 - 1731669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://medicinabuenosaires.com/revistas/vol84-24/s5/1s5.pdfInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:12:28Zoai:ri.conicet.gov.ar:11336/264230instacron: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 10:12:28.285CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv BMP7 promotes cisplatin chemoresistance of cervical cancer cells through the PI3K/AKT signaling pathway
title BMP7 promotes cisplatin chemoresistance of cervical cancer cells through the PI3K/AKT signaling pathway
spellingShingle BMP7 promotes cisplatin chemoresistance of cervical cancer cells through the PI3K/AKT signaling pathway
Birkenstok, Cintia Noelia
BMP7
CISPLATIN
CHEMORESISTANCE
CERVICAL CANCER
title_short BMP7 promotes cisplatin chemoresistance of cervical cancer cells through the PI3K/AKT signaling pathway
title_full BMP7 promotes cisplatin chemoresistance of cervical cancer cells through the PI3K/AKT signaling pathway
title_fullStr BMP7 promotes cisplatin chemoresistance of cervical cancer cells through the PI3K/AKT signaling pathway
title_full_unstemmed BMP7 promotes cisplatin chemoresistance of cervical cancer cells through the PI3K/AKT signaling pathway
title_sort BMP7 promotes cisplatin chemoresistance of cervical cancer cells through the PI3K/AKT signaling pathway
dc.creator.none.fl_str_mv Birkenstok, Cintia Noelia
Carriere, Pedro Matias
Novoa Díaz, María Belén
Zwenger, Ariel
Gentili, Claudia Rosana
Calvo, Natalia Graciela
author Birkenstok, Cintia Noelia
author_facet Birkenstok, Cintia Noelia
Carriere, Pedro Matias
Novoa Díaz, María Belén
Zwenger, Ariel
Gentili, Claudia Rosana
Calvo, Natalia Graciela
author_role author
author2 Carriere, Pedro Matias
Novoa Díaz, María Belén
Zwenger, Ariel
Gentili, Claudia Rosana
Calvo, Natalia Graciela
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv BMP7
CISPLATIN
CHEMORESISTANCE
CERVICAL CANCER
topic BMP7
CISPLATIN
CHEMORESISTANCE
CERVICAL CANCER
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Chemotherapy with cisplatin is one of the standard treatments for patients with advanced or recurrent cervical cancer (CC). However, chemoresistance can develop, compromising its efficacy in clinical practice. We previously observed an indirect role of bone morphogenetic protein 7 (BMP7) in cisplatin chemoresistance and in processes associated with cell plasticity in CC by acting on endothelial cells. In this work, the objective was to investigate a direct role of BMP7 in chemoresistance to cisplatin in CC and the molecular mechanisms involved. First, we evaluated the viability of both control HeLa cells and HeLa cells overexpressing BMP7, obtained via CRISPR/dCas9 technology, when exposed to different concentrations of cisplatin using the neutral red assay. Compared to control cells, BMP7-overexpressing HeLa cells exhibited higher viability under increasing concentrations of cisplatin and a higher half-maximal inhibitory concentration (IC50) of cisplatin. These results were confirmed by trypan blue dye exclusion testing. Then, we investigated the impact of this cytokine on markers involved in apoptosis and cell cycle regulation modulated by cisplatin using Western Blot analysis. We found that overexpression of BMP7 reverses the PARP cleavage, the decrease in cyclin D1 expression, and the Akt phosphorylation induced by cisplatin in CC cells. An increase in Akt phosphorylation levels was further observed in BMP7-overexpressing cells. Finally, we employed a trypan blue assay to determine the effect of LY294002, a phosphatidylinositol-3-kinase (PI3K) inhibitor, which is a key enzyme involved in the activation of Akt, on the cell viability of CC cells. LY294002 reversed the increase in cell viability induced by BMP7 under cisplatin treatment. Taken together, these results provide evidence that BMP7 plays a significant role in cisplatin resistance in cervical cancer cells by influencing the PI3K/Akt pathway.
Fil: Birkenstok, Cintia Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Carriere, Pedro Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Novoa Díaz, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Zwenger, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gentili, Claudia Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Calvo, Natalia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
LXIX Reunión Anual de la Sociedad Argentina de Investigación Clínica y XXVI Sociedad Argentina de Fisiología
Ciudad Autónoma de Buenos Aires
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Latinoamericana de Ciencias Fisiológicas
Sociedad Argentina de Fisiología
description Chemotherapy with cisplatin is one of the standard treatments for patients with advanced or recurrent cervical cancer (CC). However, chemoresistance can develop, compromising its efficacy in clinical practice. We previously observed an indirect role of bone morphogenetic protein 7 (BMP7) in cisplatin chemoresistance and in processes associated with cell plasticity in CC by acting on endothelial cells. In this work, the objective was to investigate a direct role of BMP7 in chemoresistance to cisplatin in CC and the molecular mechanisms involved. First, we evaluated the viability of both control HeLa cells and HeLa cells overexpressing BMP7, obtained via CRISPR/dCas9 technology, when exposed to different concentrations of cisplatin using the neutral red assay. Compared to control cells, BMP7-overexpressing HeLa cells exhibited higher viability under increasing concentrations of cisplatin and a higher half-maximal inhibitory concentration (IC50) of cisplatin. These results were confirmed by trypan blue dye exclusion testing. Then, we investigated the impact of this cytokine on markers involved in apoptosis and cell cycle regulation modulated by cisplatin using Western Blot analysis. We found that overexpression of BMP7 reverses the PARP cleavage, the decrease in cyclin D1 expression, and the Akt phosphorylation induced by cisplatin in CC cells. An increase in Akt phosphorylation levels was further observed in BMP7-overexpressing cells. Finally, we employed a trypan blue assay to determine the effect of LY294002, a phosphatidylinositol-3-kinase (PI3K) inhibitor, which is a key enzyme involved in the activation of Akt, on the cell viability of CC cells. LY294002 reversed the increase in cell viability induced by BMP7 under cisplatin treatment. Taken together, these results provide evidence that BMP7 plays a significant role in cisplatin resistance in cervical cancer cells by influencing the PI3K/Akt pathway.
publishDate 2024
dc.date.none.fl_str_mv 2024
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/11336/264230
BMP7 promotes cisplatin chemoresistance of cervical cancer cells through the PI3K/AKT signaling pathway; LXIX Reunión Anual de la Sociedad Argentina de Investigación Clínica y XXVI Sociedad Argentina de Fisiología; Ciudad Autónoma de Buenos Aires; Argentina; 2024; 173 - 173
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/264230
identifier_str_mv BMP7 promotes cisplatin chemoresistance of cervical cancer cells through the PI3K/AKT signaling pathway; LXIX Reunión Anual de la Sociedad Argentina de Investigación Clínica y XXVI Sociedad Argentina de Fisiología; Ciudad Autónoma de Buenos Aires; Argentina; 2024; 173 - 173
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://medicinabuenosaires.com/revistas/vol84-24/s5/1s5.pdf
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/pdf
application/pdf
dc.coverage.none.fl_str_mv Internacional
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
_version_ 1844614032074473472
score 13.260194

Publicaciones similares