| Autor: |
Brizzolara A; IRCCS AOU San Martino Polyclinic Hospital, 16132 Genova, Italy., Garbati P; Department of Experimental Medicine (DIMES), University of Genova, 16126 Genova, Italy., Vella S; Department 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, Italy.; Anemocyte S.r.l., 21040 Gerenzano, Italy., Calderoni M; Department of Experimental Medicine (DIMES), University of Genova, 16126 Genova, Italy., Quattrone A; Laboratory of Translational Genomics, Centre for Integrative Biology, University of Trento, 38123 Trento, Italy., Tonini GP; Neuroblastoma Laboratory, Pediatric Research Institute, The 'Città della Speranza' Foundation, 35128 Padua, Italy., Capasso M; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80145 Naples, Italy.; CEINGE Biotecnologie Avanzate, 80131 Naples, Italy.; SDN Research Institute Diagnostics and Nuclear, 80133 Naples, Italy., Longo L; Lung Cancer Unit, Division of Medical Oncology II, IRCCS San Martino Polyclinic Hospital, 16132 Genova, Italy., Barbieri R; Department of Experimental Medicine (DIMES), University of Genova, 16126 Genova, Italy., Florio T; IRCCS AOU San Martino Polyclinic Hospital, 16132 Genova, Italy.; Department of Internal Medicine (DIMI), University of Genova, 16126 Genova, Italy., Pagano A; IRCCS AOU San Martino Polyclinic Hospital, 16132 Genova, Italy.; Department of Experimental Medicine (DIMES), University of Genova, 16126 Genova, Italy. |
| Abstrakt: |
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. |
