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Pediatr Res. 2017 Apr 18. doi: 10.1038/pr.2017.74. [Epub ahead of print]

Novel targeted therapy for neuroblastoma: Silencing the MXD3 gene using siRNA.

Author information

1
Department of Pediatrics.
2
Stem Cell Program.
3
Department of Pediatrics, Niigata University, Japan.
4
Department of Pharmacology.
5
Department of Internal Medicine.
6
Department of Public Health Sciences.
7
Department of Biological & Agricultural Engineering, University of California, Davis, California.

Abstract

BACKGROUND:

Neuroblastoma is the second most common extracranial cancer in children. Current therapies for neuroblastoma, which use a combination of chemotherapy drugs, have limitations for high-risk subtypes and can cause significant long-term adverse effects in young patients. Therefore, a new therapy is needed. In this study, we investigated the transcription factor MXD3 as a potential therapeutic target in neuroblastoma.

METHODS:

MXD3 expression was analyzed in five neuroblastoma cell lines by immunocytochemistry and quantitative real time reverse transcription PCR and in 18 primary patient tumor samples by immunohistochemistry. We developed nanocomplexes using siRNA and superparamagnetic iron oxide nanoparticles to target MXD3 in neuroblastoma cell lines in vitro as a single agent therapeutic and in combination with doxorubicin, vincristine, cisplatin, or maphosphamide, common drugs used in current neuroblastoma treatment.

RESULTS:

MXD3 was highly expressed in neuroblastoma cell lines and in patient tumors that had high-risk features. Neuroblastoma cells treated in vitro with the MXD3 siRNA nanocomplexes showed MXD3 protein knockdown and resulted in cell apoptosis. Furthermore, combining MXD3 siRNA nanocomplexes with each of the four drugs, all showed additive efficacy.

CONCLUSIONS:

These results indicate that MXD3 is a potential new target and MXD3 siRNA nanocomplexes are a novel therapeutic approach for neuroblastoma.Pediatric Research accepted article preview online, 18 April 2017. doi:10.1038/pr.2017.74.

PMID:
28419087
DOI:
10.1038/pr.2017.74
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