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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MDPI AG
2020-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/22/5234 |
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| author | Antonella Brizzolara Patrizia Garbati Serena Vella Matilde Calderoni Alessandro Quattrone Gian Paolo Tonini Mario Capasso Luca Longo Raffaella Barbieri Tullio Florio Aldo Pagano |
| author_facet | Antonella Brizzolara Patrizia Garbati Serena Vella Matilde Calderoni Alessandro Quattrone Gian Paolo Tonini Mario Capasso Luca Longo Raffaella Barbieri Tullio Florio Aldo Pagano |
| author_sort | Antonella Brizzolara |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T14:57:40Z |
| format | Article |
| id | doaj.art-34a0af31801e4f8780e72203e9923615 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T14:57:40Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-34a0af31801e4f8780e72203e99236152023-11-20T20:26:25ZengMDPI AGMolecules1420-30492020-11-012522523410.3390/molecules25225234Co-Administration of Fendiline Hydrochloride Enhances Chemotherapeutic Efficacy of Cisplatin in Neuroblastoma TreatmentAntonella Brizzolara0Patrizia Garbati1Serena Vella2Matilde Calderoni3Alessandro Quattrone4Gian Paolo Tonini5Mario Capasso6Luca Longo7Raffaella Barbieri8Tullio Florio9Aldo Pagano10IRCCS AOU San Martino Polyclinic Hospital, 16132 Genova, ItalyDepartment of Experimental Medicine (DIMES), University of Genova, 16126 Genova, ItalyDepartment of Laboratory Medicine and Advanced Biotechnologies, Institute of Hospitalization and Care of a Scientific Nature—Mediterranean Institute for Transplantation and Highly Specialized Therapies (IRCCS- ISMETT), 90127 Palermo, ItalyDepartment of Experimental Medicine (DIMES), University of Genova, 16126 Genova, ItalyLaboratory of Translational Genomics, Centre for Integrative Biology, University of Trento, 38123 Trento, ItalyNeuroblastoma Laboratory, Pediatric Research Institute, The “Città della Speranza” Foundation, 35128 Padua, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80145 Naples, ItalyLung Cancer Unit, Division of Medical Oncology II, IRCCS San Martino Polyclinic Hospital, 16132 Genova, ItalyDepartment of Experimental Medicine (DIMES), University of Genova, 16126 Genova, ItalyIRCCS AOU San Martino Polyclinic Hospital, 16132 Genova, ItalyIRCCS AOU San Martino Polyclinic Hospital, 16132 Genova, ItalyDespite 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.https://www.mdpi.com/1420-3049/25/22/5234neuroblastomanon-coding RNANDM29fendiline hydrochlorideGD2 |
| spellingShingle | Antonella Brizzolara Patrizia Garbati Serena Vella Matilde Calderoni Alessandro Quattrone Gian Paolo Tonini Mario Capasso Luca Longo Raffaella Barbieri Tullio Florio Aldo Pagano Co-Administration of Fendiline Hydrochloride Enhances Chemotherapeutic Efficacy of Cisplatin in Neuroblastoma Treatment Molecules neuroblastoma non-coding RNA NDM29 fendiline hydrochloride GD2 |
| 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 | neuroblastoma non-coding RNA NDM29 fendiline hydrochloride GD2 |
| url | https://www.mdpi.com/1420-3049/25/22/5234 |
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