Literature DB >> 29423589

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

Tomomasa Hiramatsu1, Jyoji Yoshizawa2, Kazuaki Miyaguni2, Tetsuro Sugihara2, Atsushi Harada2, Sayuri Kaji2, Goki Uchida2, Daisuke Kanamori2, Yuji Baba2, Shuichi Ashizuka2, Takao Ohki2.   

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.

Entities:  

Keywords:  Apoptosis; C1300; Etoposide; NF-κB; Neuroblastoma; Thalidomide

Mesh:

Substances:

Year:  2018        PMID: 29423589     DOI: 10.1007/s00383-018-4234-4

Source DB:  PubMed          Journal:  Pediatr Surg Int        ISSN: 0179-0358            Impact factor:   1.827


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