TY - JOUR
T1 - Mcm2 and carbonic anhydrase 9 are novel potential targets for neuroblastoma pharmacological treatment
AU - Garbati, Patrizia
AU - Barbieri, Raffaella
AU - Cangelosi, Davide
AU - Zanon, Carlo
AU - Costa, Delfina
AU - Eva, Alessandra
AU - Thellung, Stefano
AU - Calderoni, Matilde
AU - Baldini, Francesca
AU - Tonini, Gian Paolo
AU - Modesto, Paola
AU - Florio, Tullio
AU - Pagano, Aldo
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Acetazolamide
KW - Carbonic anhydrase 9
KW - Ciprofloxacin
KW - MCM2
KW - Neuroblastoma
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U2 - 10.3390/biomedicines8110471
DO - 10.3390/biomedicines8110471
M3 - Article
AN - SCOPUS:85097268007
VL - 8
SP - 1
EP - 19
JO - Biomedicines
JF - Biomedicines
SN - 2227-9059
IS - 11
M1 - 471
ER -