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MCM2 and Carbonic Anhydrase 9 Are Novel Potential Targets for Neuroblastoma Pharmacological Treatment

Authors :
Patrizia Garbati
Raffaella Barbieri
Davide Cangelosi
Carlo Zanon
Delfina Costa
Alessandra Eva
Stefano Thellung
Matilde Calderoni
Francesca Baldini
Gian Paolo Tonini
Paola Modesto
Tullio Florio
Aldo Pagano
Source :
Biomedicines, Vol 8, Iss 11, p 471 (2020)
Publication Year :
2020
Publisher :
MDPI AG, 2020.

Abstract

To overcome the lack of effective pharmacological treatments for high-risk neuroblastoma (HR-NB), the development of novel in vitro and in vivo models that better recapitulate the disease is required. Here, we used an in vitro multiclonal cell model encompassing NB cell differentiation stages, to identify potential novel pharmacological targets. This model allowed us to identify, by low-density RT-PCR arrays, two gene sets, one over-expressed during NB cell differentiation, and the other up-regulated in more malignant cells. Challenging two HR-NB gene expression datasets, we found that these two gene sets are related to high and low survival, respectively. Using mouse NB cisplatin-treated xenografts, we identified two genes within the list associated to the malignant stage (MCM2 and carbonic anhydrase 9), whose expression is positively correlated with tumor growth. Thus, we tested their pharmacological targeting as potential therapeutic strategy. We measured mice survival and tumor growth rate after xenografts of human NB treated with cisplatin in the presence of MCM2/carbonic anhydrase 9 inhibitors (ciprofloxacin and acetazolamide). MCM2 or carbonic anhydrase 9 inhibition significantly increased cisplatin activity, supporting their possible testing for NB therapy.

Details

Language :
English
ISSN :
22279059
Volume :
8
Issue :
11
Database :
Directory of Open Access Journals
Journal :
Biomedicines
Publication Type :
Academic Journal
Accession number :
edsdoj.71dee4b2016a44b395e9e6cb7320f7f7
Document Type :
article
Full Text :
https://doi.org/10.3390/biomedicines8110471