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

Connie Duong, Sakiko Yoshida, Cathy Chen, Gustavo Barisone, Elva D Diaz, Yueju Li, Laurel A Beckett, Jong Hee Chung, Reuben Antony, Jan Nolta, Nitin Nitin, Noriko Satake

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

BackgroundNeuroblastoma 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.MethodsMXD3 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.ResultsMXD3 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.ConclusionThese results indicate that MXD3 is a potential new target and that the use of MXD3 siRNA nanocomplexes is a novel therapeutic approach for neuroblastoma.

Original languageEnglish (US)
Pages (from-to)527-535
Number of pages9
JournalPediatric Research
Volume82
Issue number3
DOIs
StatePublished - Sep 1 2017

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Gene Silencing
Neuroblastoma
Small Interfering RNA
Therapeutics
Cell Line
Immunohistochemistry
Pharmaceutical Preparations
Neoplasms
Vincristine
Combination Drug Therapy
Nanoparticles
Doxorubicin
Cisplatin
Reverse Transcription
Transcription Factors
Apoptosis
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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Novel targeted therapy for neuroblastoma : Silencing the MXD3 gene using siRNA. / Duong, Connie; Yoshida, Sakiko; Chen, Cathy; Barisone, Gustavo; Diaz, Elva D; Li, Yueju; Beckett, Laurel A; Chung, Jong Hee; Antony, Reuben; Nolta, Jan; Nitin, Nitin; Satake, Noriko.

In: Pediatric Research, Vol. 82, No. 3, 01.09.2017, p. 527-535.

Research output: Contribution to journalArticle

Duong, Connie ; Yoshida, Sakiko ; Chen, Cathy ; Barisone, Gustavo ; Diaz, Elva D ; Li, Yueju ; Beckett, Laurel A ; Chung, Jong Hee ; Antony, Reuben ; Nolta, Jan ; Nitin, Nitin ; Satake, Noriko. / Novel targeted therapy for neuroblastoma : Silencing the MXD3 gene using siRNA. In: Pediatric Research. 2017 ; Vol. 82, No. 3. pp. 527-535.
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abstract = "BackgroundNeuroblastoma 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.MethodsMXD3 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.ResultsMXD3 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.ConclusionThese 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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AB - BackgroundNeuroblastoma 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.MethodsMXD3 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.ResultsMXD3 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.ConclusionThese 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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