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Authordc.contributor.authorRocha Pérez, José Dellis
Authordc.contributor.authorUribe, Daniel
Authordc.contributor.authorDelgado, Javiera
Authordc.contributor.authorNiechi Gaete, Ignacio Alfredo
Authordc.contributor.authorAlarcón, Sebastián
Authordc.contributor.authorErices, José Ignacio
Authordc.contributor.authorMelo Monsalve, Rómulo Eduardo
Authordc.contributor.authorFernández Gajardo, Rodrigo Alfredo
Authordc.contributor.authorSalazar Onfray, Flavio Andrés
Authordc.contributor.authorSan Martín, Rody
Authordc.contributor.authorQuezada Monrás, Claudia Andrea
Admission datedc.date.accessioned2023-01-23T21:09:10Z
Available datedc.date.available2023-01-23T21:09:10Z
Publication datedc.date.issued2022
Cita de ítemdc.identifier.citationInt. J. Mol. Sci. 2022, 23, 9022.es_ES
Identifierdc.identifier.other10.3390/ijms23169022
Identifierdc.identifier.urihttps://repositorio.uchile.cl/handle/2250/191719
Abstractdc.description.abstractGlioblastoma is the most common and aggressive primary brain tumor, characterized by its high chemoresistance and the presence of a cell subpopulation that persists under hypoxic niches, called glioblastoma stem-like cells (GSCs). The chemoresistance of GSCs is mediated in part by adenosine signaling and ABC transporters, which extrude drugs outside the cell, such as the multidrug resistance-associated proteins (MRPs) subfamily. Adenosine promotes MRP1-dependent chemoresistance under normoxia. However, adenosine/MRPs-dependent chemoresistance under hypoxia has not been studied until now. Transcript and protein levels were determined by RTqPCR and Western blot, respectively. MRP extrusion capacity was determined by intracellular 5 (6)-Carboxyfluorescein diacetate (CFDA) accumulation. Cell viability was measured by MTS assays. Cell cycle and apoptosis were determined by flow cytometry. Here, we show for the first time that MRP3 expression is induced under hypoxia through the A2B adenosine receptor. Hypoxia enhances MRP-dependent extrusion capacity and the chemoresistance of GSCs. Meanwhile, MRP3 knockdown decreases GSC viability under hypoxia. Downregulation of the A2B receptor decreases MRP3 expression and chemosensibilizes GSCs treated with teniposide under hypoxia. These data suggest that hypoxia-dependent activation of A2B adenosine receptor promotes survival of GSCs through MRP3 induction.es_ES
Patrocinadordc.description.sponsorshipComision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1200885 1160777 1211613 3180621 3170851 Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) 21150719 21140446 Agencia Nacional de Investigacion y Desarrollo (ANID)-Millennium Science Initiative Program ICN09_016/ICN 2021_045 Agencia Nacional de Investigacion y Desarrollo (ANID)-Millennium Institute of Immunology and Immunotherapy ICN09_016/ICN 2021_045es_ES
Lenguagedc.language.isoenes_ES
Publisherdc.publisherMDPIes_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
Link to Licensedc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
Sourcedc.sourceInternational Journal of Molecular Scienceses_ES
Keywordsdc.subjectMRP3es_ES
Keywordsdc.subjectAdenosinees_ES
Keywordsdc.subjectA2Bes_ES
Keywordsdc.subjectGlioblastomaes_ES
Keywordsdc.subjectChemoresistancees_ES
Keywordsdc.subjectGSCses_ES
Keywordsdc.subjectHypoxiaes_ES
Títulodc.titleA2B adenosine receptor enhances chemoresistance of glioblastoma stem-like cells under hypoxia: new insights into MRP3 transporter functiones_ES
Document typedc.typeArtículo de revistaes_ES
dc.description.versiondc.description.versionVersión publicada - versión final del editores_ES
dcterms.accessRightsdcterms.accessRightsAcceso abiertoes_ES
Catalogueruchile.catalogadorcfres_ES
Indexationuchile.indexArtículo de publícación WoSes_ES


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Attribution-NonCommercial-NoDerivs 3.0 United States
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 United States