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Thalidomide potentiates etoposide-induced apoptosis in murine neuroblastoma through suppression of NF-κB activation

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Abstract

Purpose

Treatment for high-risk neuroblastoma is still challenging. The purpose of the present study was to determine whether thalidomide suppresses etoposide-induced NF-κB activation and thus potentiates apoptosis in murine neuroblastoma.

Methods

A murine neuroblastoma cell line, C1300, and A/J mice were used in this study. We evaluated NF-κB activation after using etoposide with or without thalidomide by quantitative analysis of NF-κB by ELISA and by Western blot analysis of IκB phosphorylation in vitro and in vivo. Induction of apoptosis was evaluated by Western blot analysis of the apoptotic signals caspase-3, 8, and 9 in vitro and by TUNEL assays in vivo. We also evaluated the efficacy of the combination of etoposide and thalidomide by assessing tumor growth and mouse survival in vivo.

Results

Etoposide activated NF-κB in C1300 cells. This activation was suppressed by thalidomide and IκB was re-upregulated. The apoptotic signals were enhanced by the combination of thalidomide and etoposide compared with etoposide alone in vitro, which was consistent with TUNEL assays. The combination of etoposide and thalidomide also slowed tumor growth and mouse survival.

Conclusion

Thalidomide potentiates etoposide-induced apoptosis in murine neuroblastoma by suppressing NF-κB.

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Acknowledgements

The authors thank Mimi Zeiger, MA, University of California, San Francisco, for editorial assistance, Rei Kudo, MD, PhD, for conceptional advice, and Takashi Horiuchi, MD and Hiroshi Sugano, MD for technical support.

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Authors and Affiliations

  1. Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan

    Tomomasa Hiramatsu, Jyoji Yoshizawa, Kazuaki Miyaguni, Tetsuro Sugihara, Atsushi Harada, Sayuri Kaji, Goki Uchida, Daisuke Kanamori, Yuji Baba, Shuichi Ashizuka & Takao Ohki

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  1. Tomomasa Hiramatsu
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  2. Jyoji Yoshizawa
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Correspondence to Tomomasa Hiramatsu.

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Hiramatsu, T., Yoshizawa, J., Miyaguni, K. et al. Thalidomide potentiates etoposide-induced apoptosis in murine neuroblastoma through suppression of NF-κB activation. Pediatr Surg Int 34, 443–450 (2018). https://doi.org/10.1007/s00383-018-4234-4

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