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Combined Treatment with Doxorubicin and Rapamycin Is Effective against In Vitro and In Vivo Models of Human Glioblastoma

Despite numerous clinical trials, glioblastoma (GBM) remains a tumor that is difficult to treat. The aim of this study was to investigate the potential of a new pharmacological approach, combining doxorubicin (Dox) and rapamycin (Rapa), in in vitro and in vivo GBM models. Cytotoxic and anti-prolifer...

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Autores principales: Iorio, Anna Lisa, Da Ros, Martina, Pisano, Claudio, de Martino, Maurizio, Genitori, Lorenzo, Sardi, Iacopo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462908/
https://www.ncbi.nlm.nih.gov/pubmed/30857276
http://dx.doi.org/10.3390/jcm8030331
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author Iorio, Anna Lisa
Da Ros, Martina
Pisano, Claudio
de Martino, Maurizio
Genitori, Lorenzo
Sardi, Iacopo
author_facet Iorio, Anna Lisa
Da Ros, Martina
Pisano, Claudio
de Martino, Maurizio
Genitori, Lorenzo
Sardi, Iacopo
author_sort Iorio, Anna Lisa
collection PubMed
description Despite numerous clinical trials, glioblastoma (GBM) remains a tumor that is difficult to treat. The aim of this study was to investigate the potential of a new pharmacological approach, combining doxorubicin (Dox) and rapamycin (Rapa), in in vitro and in vivo GBM models. Cytotoxic and anti-proliferative effects of Rapa plus Dox treatments were analyzed in GBM cell lines. The in vivo effectiveness of these treatments was investigated in an orthotopic xenograft mice model of GBM. In vitro results demonstrated that prolonged exposure to Rapa sensitize GBM cells to Dox treatments. In vivo results demonstrated that Rapa (5 mg/kg) plus Dox (5 mg/kg) determined the major tumor growth inhibition (−97.29% vs. control) but results in greater toxicity. The combination Rapa plus Dox (2.5 mg/kg) showed a tumor inhibition like Rapa plus Dox (5 mg/kg) with a toxicity comparable to Rapa alone. Thus, this study demonstrated the efficacy of this pharmacological approach, providing the rationale for a clinical application of this combinational therapy in “poor-responder” GBM patients.
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spelling pubmed-64629082019-04-19 Combined Treatment with Doxorubicin and Rapamycin Is Effective against In Vitro and In Vivo Models of Human Glioblastoma Iorio, Anna Lisa Da Ros, Martina Pisano, Claudio de Martino, Maurizio Genitori, Lorenzo Sardi, Iacopo J Clin Med Article Despite numerous clinical trials, glioblastoma (GBM) remains a tumor that is difficult to treat. The aim of this study was to investigate the potential of a new pharmacological approach, combining doxorubicin (Dox) and rapamycin (Rapa), in in vitro and in vivo GBM models. Cytotoxic and anti-proliferative effects of Rapa plus Dox treatments were analyzed in GBM cell lines. The in vivo effectiveness of these treatments was investigated in an orthotopic xenograft mice model of GBM. In vitro results demonstrated that prolonged exposure to Rapa sensitize GBM cells to Dox treatments. In vivo results demonstrated that Rapa (5 mg/kg) plus Dox (5 mg/kg) determined the major tumor growth inhibition (−97.29% vs. control) but results in greater toxicity. The combination Rapa plus Dox (2.5 mg/kg) showed a tumor inhibition like Rapa plus Dox (5 mg/kg) with a toxicity comparable to Rapa alone. Thus, this study demonstrated the efficacy of this pharmacological approach, providing the rationale for a clinical application of this combinational therapy in “poor-responder” GBM patients. MDPI 2019-03-09 /pmc/articles/PMC6462908/ /pubmed/30857276 http://dx.doi.org/10.3390/jcm8030331 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Iorio, Anna Lisa
Da Ros, Martina
Pisano, Claudio
de Martino, Maurizio
Genitori, Lorenzo
Sardi, Iacopo
Combined Treatment with Doxorubicin and Rapamycin Is Effective against In Vitro and In Vivo Models of Human Glioblastoma
title Combined Treatment with Doxorubicin and Rapamycin Is Effective against In Vitro and In Vivo Models of Human Glioblastoma
title_full Combined Treatment with Doxorubicin and Rapamycin Is Effective against In Vitro and In Vivo Models of Human Glioblastoma
title_fullStr Combined Treatment with Doxorubicin and Rapamycin Is Effective against In Vitro and In Vivo Models of Human Glioblastoma
title_full_unstemmed Combined Treatment with Doxorubicin and Rapamycin Is Effective against In Vitro and In Vivo Models of Human Glioblastoma
title_short Combined Treatment with Doxorubicin and Rapamycin Is Effective against In Vitro and In Vivo Models of Human Glioblastoma
title_sort combined treatment with doxorubicin and rapamycin is effective against in vitro and in vivo models of human glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462908/
https://www.ncbi.nlm.nih.gov/pubmed/30857276
http://dx.doi.org/10.3390/jcm8030331
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