Novel targeted therapy for neuroblastoma: silencing the MXD3 gene using siRNA

作者：Duong Connie; Yoshida Sakiko; Chen Cathy; Barisone Gustavo; Diaz Elva; Li Yueju; Beckett Laurel; Chung Jong; Antony Reuben; Nolta Jan; Nitin Nitin; Satake Noriko

来源：Pediatric Research, 2017, 82(3): 527-535.

DOI：10.1038/pr.2017.74

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 superpararnagnetic 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.

• 出版日期2017-9