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, on combining MXD3 siRNA nanocomplexes with each of the four drugs, all showed additive efficacy.
Conclusion
These results indicate that MXD3 is a potential new target and that the use of MXD3 siRNA nanocomplexes is a novel therapeutic approach for neuroblastoma.
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Acknowledgements
We thank Wassim N. Hmeidan and Amanda R. Favila for technical assistance on the experiments and formulating figures and a table.
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STATEMENT OF FINANCIAL SUPPORT
This work was supported by research funding from the Keaton Raphael Memorial Foundation, The Hartwell Foundation, Hyundai Hope on Wheels, National Center for Advancing Translational Sciences, NIH, through Grant #UL1 TR000002, and CTSC-MCRTP (Satake) and the California Institute for Regenerative Medicine, and NIH Transformative Grant R01GM099688 (Nolta). Statistical support was provided through the Biostatistics Shared Resource, UC Davis Comprehensive Cancer Center Support Grant P30CA093373-04.
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Duong, C., Yoshida, S., Chen, C. et al. Novel targeted therapy for neuroblastoma: silencing the MXD3 gene using siRNA. Pediatr Res 82, 527–535 (2017). https://doi.org/10.1038/pr.2017.74
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DOI: https://doi.org/10.1038/pr.2017.74
