| Autor: |
Garbati P; IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy., Barbieri R; IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy., Calderoni M; Department of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy., Baldini F; Department of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy., Nizzari M; Department of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy., Modesto P; National Reference Center for Veterinary and Comparative Oncology-Veterinary Medical Research Institute for Piemonte, Liguria and Valle d'Aosta, 10154 Torino, Italy., Florio T; IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.; Department of Internal Medicine and Centre of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy., Pagano A; IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.; Department of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy. |
| Abstrakt: |
High-risk neuroblastoma (HR-NB) still remains the most dangerous tumor in early childhood. For this reason, the identification of new therapeutic approaches is of fundamental importance. Recently, we combined the conventional pharmacological approach to NB, represented by cisplatin, with fendiline hydrochloride, an inhibitor of several transporters involved in multidrug resistance of cancer cells, which demonstrated an enhancement of the ability of cisplatin to induce apoptosis. In this work, we co-administrated acetazolamide, a carbonic anhydrase isoform IX (CAIX) inhibitor which was reported to increase chemotherapy efficacy in various cancer types, to the cisplatin/fendiline approach in SKNBE2 xenografts in NOD-SCID mice with the aim of identifying a novel and more effective treatment. We observed that the combination of the three drugs increases more than twelvefold the differences in the cytotoxic activity of cisplatin alone, leading to a remarkable decrease of the expression of malignancy markers. Our conclusion is that this approach, based on three FDA-approved drugs, may constitute an appropriate improvement of the pharmacological approach to HR-NB. |
