Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic Therapy

Autores
Olthoff, Karen Jacqueline; Nigra, Ayelén Denise; Milla Sanabria, Laura Natalia
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Glioblastoma (GBM) is the most common and deadly type of brain cancer in adults. Dysregulation of receptor tyrosine kinase pathways, such as the epidermal growth factor receptor (EGFR), contributes to therapeutic resistance. Drugs that inhibit tyrosine kinase activity and monoclonal antibodies against EGFR are strategies used in clinical trials. Photodynamic therapy (PDT) is a tumor treatment that involves the administration of a photosensitizing drug, followed by its activation with visible light, which causes cell death due to oxidative stress. Although PDT helps prolong median survival in patients with GBM, complete remission has not been achieved. Populations of GBM cells have been obtained from the T98G line resistant to PDT with methyl-5-aminolevulinic acid (Me-ALA) for characterization, comparing them with the original parental population. Objective: The objective of this work was to evaluate the general response of T98G GBM cells resistant to PDT when EGFR activity is inhibited with the drug erlotinib. Methods and Results: It has been observed that the administration of the EGFR inhibitor drug in combination with PDT reduced viability (MTT) in resistant populations compared to PDT alone. Furthermore, the PpIX content (flow cytometry) was increased in the resistant population when cells were incubated with Me-ALA and erlotinib. Erlotinib prevented cell proliferation of parental and resistant spheroids. Wound closure was reduced in both parental and PDT-resistant populations. Conclusions: Our results indicate that EGFR activation would be relevant in the resistance of GBM cells to PDT.
Fil: Olthoff, Karen Jacqueline. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
Fil: Nigra, Ayelén Denise. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
Fil: Milla Sanabria, Laura Natalia. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
Materia
GLIOBLASTOMA
PHOTODYNAMIC THERAPY
RESISTANCE
EGFR
ERLOTINIB
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/259382
Acceder
id CONICETDig_eded2354100dfe6dcfc838981d84420e
oai_identifier_str oai:ri.conicet.gov.ar:11336/259382
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic TherapyOlthoff, Karen JacquelineNigra, Ayelén DeniseMilla Sanabria, Laura NataliaGLIOBLASTOMAPHOTODYNAMIC THERAPYRESISTANCEEGFRERLOTINIBhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Background: Glioblastoma (GBM) is the most common and deadly type of brain cancer in adults. Dysregulation of receptor tyrosine kinase pathways, such as the epidermal growth factor receptor (EGFR), contributes to therapeutic resistance. Drugs that inhibit tyrosine kinase activity and monoclonal antibodies against EGFR are strategies used in clinical trials. Photodynamic therapy (PDT) is a tumor treatment that involves the administration of a photosensitizing drug, followed by its activation with visible light, which causes cell death due to oxidative stress. Although PDT helps prolong median survival in patients with GBM, complete remission has not been achieved. Populations of GBM cells have been obtained from the T98G line resistant to PDT with methyl-5-aminolevulinic acid (Me-ALA) for characterization, comparing them with the original parental population. Objective: The objective of this work was to evaluate the general response of T98G GBM cells resistant to PDT when EGFR activity is inhibited with the drug erlotinib. Methods and Results: It has been observed that the administration of the EGFR inhibitor drug in combination with PDT reduced viability (MTT) in resistant populations compared to PDT alone. Furthermore, the PpIX content (flow cytometry) was increased in the resistant population when cells were incubated with Me-ALA and erlotinib. Erlotinib prevented cell proliferation of parental and resistant spheroids. Wound closure was reduced in both parental and PDT-resistant populations. Conclusions: Our results indicate that EGFR activation would be relevant in the resistance of GBM cells to PDT.Fil: Olthoff, Karen Jacqueline. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaFil: Nigra, Ayelén Denise. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaFil: Milla Sanabria, Laura Natalia. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaMDPI2024-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/259382Olthoff, Karen Jacqueline; Nigra, Ayelén Denise; Milla Sanabria, Laura Natalia; Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic Therapy; MDPI; Brain Sciences; 14; 12; 11-2024; 1-162076-3425CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2076-3425/14/12/1192info:eu-repo/semantics/altIdentifier/doi/10.3390/brainsci14121192info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:16:06Zoai:ri.conicet.gov.ar:11336/259382instacron: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 15:16:07.199CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic Therapy
title Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic Therapy
spellingShingle Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic Therapy
Olthoff, Karen Jacqueline
GLIOBLASTOMA
PHOTODYNAMIC THERAPY
RESISTANCE
EGFR
ERLOTINIB
title_short Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic Therapy
title_full Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic Therapy
title_fullStr Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic Therapy
title_full_unstemmed Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic Therapy
title_sort Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic Therapy
dc.creator.none.fl_str_mv Olthoff, Karen Jacqueline
Nigra, Ayelén Denise
Milla Sanabria, Laura Natalia
author Olthoff, Karen Jacqueline
author_facet Olthoff, Karen Jacqueline
Nigra, Ayelén Denise
Milla Sanabria, Laura Natalia
author_role author
author2 Nigra, Ayelén Denise
Milla Sanabria, Laura Natalia
author2_role author
author
dc.subject.none.fl_str_mv GLIOBLASTOMA
PHOTODYNAMIC THERAPY
RESISTANCE
EGFR
ERLOTINIB
topic GLIOBLASTOMA
PHOTODYNAMIC THERAPY
RESISTANCE
EGFR
ERLOTINIB
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Glioblastoma (GBM) is the most common and deadly type of brain cancer in adults. Dysregulation of receptor tyrosine kinase pathways, such as the epidermal growth factor receptor (EGFR), contributes to therapeutic resistance. Drugs that inhibit tyrosine kinase activity and monoclonal antibodies against EGFR are strategies used in clinical trials. Photodynamic therapy (PDT) is a tumor treatment that involves the administration of a photosensitizing drug, followed by its activation with visible light, which causes cell death due to oxidative stress. Although PDT helps prolong median survival in patients with GBM, complete remission has not been achieved. Populations of GBM cells have been obtained from the T98G line resistant to PDT with methyl-5-aminolevulinic acid (Me-ALA) for characterization, comparing them with the original parental population. Objective: The objective of this work was to evaluate the general response of T98G GBM cells resistant to PDT when EGFR activity is inhibited with the drug erlotinib. Methods and Results: It has been observed that the administration of the EGFR inhibitor drug in combination with PDT reduced viability (MTT) in resistant populations compared to PDT alone. Furthermore, the PpIX content (flow cytometry) was increased in the resistant population when cells were incubated with Me-ALA and erlotinib. Erlotinib prevented cell proliferation of parental and resistant spheroids. Wound closure was reduced in both parental and PDT-resistant populations. Conclusions: Our results indicate that EGFR activation would be relevant in the resistance of GBM cells to PDT.
Fil: Olthoff, Karen Jacqueline. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
Fil: Nigra, Ayelén Denise. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
Fil: Milla Sanabria, Laura Natalia. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
description Background: Glioblastoma (GBM) is the most common and deadly type of brain cancer in adults. Dysregulation of receptor tyrosine kinase pathways, such as the epidermal growth factor receptor (EGFR), contributes to therapeutic resistance. Drugs that inhibit tyrosine kinase activity and monoclonal antibodies against EGFR are strategies used in clinical trials. Photodynamic therapy (PDT) is a tumor treatment that involves the administration of a photosensitizing drug, followed by its activation with visible light, which causes cell death due to oxidative stress. Although PDT helps prolong median survival in patients with GBM, complete remission has not been achieved. Populations of GBM cells have been obtained from the T98G line resistant to PDT with methyl-5-aminolevulinic acid (Me-ALA) for characterization, comparing them with the original parental population. Objective: The objective of this work was to evaluate the general response of T98G GBM cells resistant to PDT when EGFR activity is inhibited with the drug erlotinib. Methods and Results: It has been observed that the administration of the EGFR inhibitor drug in combination with PDT reduced viability (MTT) in resistant populations compared to PDT alone. Furthermore, the PpIX content (flow cytometry) was increased in the resistant population when cells were incubated with Me-ALA and erlotinib. Erlotinib prevented cell proliferation of parental and resistant spheroids. Wound closure was reduced in both parental and PDT-resistant populations. Conclusions: Our results indicate that EGFR activation would be relevant in the resistance of GBM cells to PDT.
publishDate 2024
dc.date.none.fl_str_mv 2024-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/259382
Olthoff, Karen Jacqueline; Nigra, Ayelén Denise; Milla Sanabria, Laura Natalia; Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic Therapy; MDPI; Brain Sciences; 14; 12; 11-2024; 1-16
2076-3425
CONICET Digital
CONICET
url http://hdl.handle.net/11336/259382
identifier_str_mv Olthoff, Karen Jacqueline; Nigra, Ayelén Denise; Milla Sanabria, Laura Natalia; Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic Therapy; MDPI; Brain Sciences; 14; 12; 11-2024; 1-16
2076-3425
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.mdpi.com/2076-3425/14/12/1192
info:eu-repo/semantics/altIdentifier/doi/10.3390/brainsci14121192
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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 13.22299

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