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Co-Administration of Fendiline Hydrochloride Enhances Chemotherapeutic Efficacy of Cisplatin in Neuroblastoma Treatment

Despite significant improvement of neuroblastoma (NB) patients’ survival due to recent treatment advancements in recent years, NB is still associated with high mortality rate. In search of novel strategies to increase NB’s susceptibility to pharmacological treatments, we investigated the in vitro an...

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Autores principales: Brizzolara, Antonella, Garbati, Patrizia, Vella, Serena, Calderoni, Matilde, Quattrone, Alessandro, Tonini, Gian Paolo, Capasso, Mario, Longo, Luca, Barbieri, Raffaella, Florio, Tullio, Pagano, Aldo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698186/
https://www.ncbi.nlm.nih.gov/pubmed/33182713
http://dx.doi.org/10.3390/molecules25225234
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author Brizzolara, Antonella
Garbati, Patrizia
Vella, Serena
Calderoni, Matilde
Quattrone, Alessandro
Tonini, Gian Paolo
Capasso, Mario
Longo, Luca
Barbieri, Raffaella
Florio, Tullio
Pagano, Aldo
author_facet Brizzolara, Antonella
Garbati, Patrizia
Vella, Serena
Calderoni, Matilde
Quattrone, Alessandro
Tonini, Gian Paolo
Capasso, Mario
Longo, Luca
Barbieri, Raffaella
Florio, Tullio
Pagano, Aldo
author_sort Brizzolara, Antonella
collection PubMed
description Despite significant improvement of neuroblastoma (NB) patients’ survival due to recent treatment advancements in recent years, NB is still associated with high mortality rate. In search of novel strategies to increase NB’s susceptibility to pharmacological treatments, we investigated the in vitro and in vivo effects of fendiline hydrochloride as an enhancer of cisplatin antitumor activity. To assess the modulation of fendiline treatment on cisplatin responses, we used in vitro (evaluating NB cell proliferation by XCELLigence technology and colony formation, and gene expression by RT-PCR) and in vivo (NB cell grafts in NOD-SCID mice) models of NB. NB cell treatment with fendiline induced the expression of the ncRNA NDM29, leading to cell differentiation and to the reduction of the expression of MDRs/ABC transporters linked to multidrug resistance. These events were correlated to higher NB cell susceptibility to cisplatin and, consequently, increased its cytotoxic potency. In vivo, this drug interaction causes an enhanced ability of cisplatin to induce apoptosis in NB masses, resulting in tumor growth reduction and prolonged animal survival rate. Thus, the administration of fendiline might be a possible novel therapeutic approach to increase cisplatin efficacy in aggressive and poorly responsive NB cases.
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spelling pubmed-76981862020-11-29 Co-Administration of Fendiline Hydrochloride Enhances Chemotherapeutic Efficacy of Cisplatin in Neuroblastoma Treatment Brizzolara, Antonella Garbati, Patrizia Vella, Serena Calderoni, Matilde Quattrone, Alessandro Tonini, Gian Paolo Capasso, Mario Longo, Luca Barbieri, Raffaella Florio, Tullio Pagano, Aldo Molecules Article Despite significant improvement of neuroblastoma (NB) patients’ survival due to recent treatment advancements in recent years, NB is still associated with high mortality rate. In search of novel strategies to increase NB’s susceptibility to pharmacological treatments, we investigated the in vitro and in vivo effects of fendiline hydrochloride as an enhancer of cisplatin antitumor activity. To assess the modulation of fendiline treatment on cisplatin responses, we used in vitro (evaluating NB cell proliferation by XCELLigence technology and colony formation, and gene expression by RT-PCR) and in vivo (NB cell grafts in NOD-SCID mice) models of NB. NB cell treatment with fendiline induced the expression of the ncRNA NDM29, leading to cell differentiation and to the reduction of the expression of MDRs/ABC transporters linked to multidrug resistance. These events were correlated to higher NB cell susceptibility to cisplatin and, consequently, increased its cytotoxic potency. In vivo, this drug interaction causes an enhanced ability of cisplatin to induce apoptosis in NB masses, resulting in tumor growth reduction and prolonged animal survival rate. Thus, the administration of fendiline might be a possible novel therapeutic approach to increase cisplatin efficacy in aggressive and poorly responsive NB cases. MDPI 2020-11-10 /pmc/articles/PMC7698186/ /pubmed/33182713 http://dx.doi.org/10.3390/molecules25225234 Text en © 2020 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
Brizzolara, Antonella
Garbati, Patrizia
Vella, Serena
Calderoni, Matilde
Quattrone, Alessandro
Tonini, Gian Paolo
Capasso, Mario
Longo, Luca
Barbieri, Raffaella
Florio, Tullio
Pagano, Aldo
Co-Administration of Fendiline Hydrochloride Enhances Chemotherapeutic Efficacy of Cisplatin in Neuroblastoma Treatment
title Co-Administration of Fendiline Hydrochloride Enhances Chemotherapeutic Efficacy of Cisplatin in Neuroblastoma Treatment
title_full Co-Administration of Fendiline Hydrochloride Enhances Chemotherapeutic Efficacy of Cisplatin in Neuroblastoma Treatment
title_fullStr Co-Administration of Fendiline Hydrochloride Enhances Chemotherapeutic Efficacy of Cisplatin in Neuroblastoma Treatment
title_full_unstemmed Co-Administration of Fendiline Hydrochloride Enhances Chemotherapeutic Efficacy of Cisplatin in Neuroblastoma Treatment
title_short Co-Administration of Fendiline Hydrochloride Enhances Chemotherapeutic Efficacy of Cisplatin in Neuroblastoma Treatment
title_sort co-administration of fendiline hydrochloride enhances chemotherapeutic efficacy of cisplatin in neuroblastoma treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698186/
https://www.ncbi.nlm.nih.gov/pubmed/33182713
http://dx.doi.org/10.3390/molecules25225234
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