YM155 Inhibits Neuroblastoma Cell Migration and Survival <i>in Vitro</i> and Tumor Growth and Metastatic Burden in a Pre-Clinical Model — Oak Academic Publishing
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YM155 Inhibits Neuroblastoma Cell Migration and Survival <i>in Vitro</i> and Tumor Growth and Metastatic Burden in a Pre-Clinical Model
Laboratory for Translational Neuroblastoma Research, Van Andel Research Institute, Grand Rapids, USA
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Laboratory for Translational Neuroblastoma Research, Van Andel Research Institute, Grand Rapids, USA
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Laboratory for Translational Neuroblastoma Research, Van Andel Research Institute, Grand Rapids, USA
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Laboratory for Translational Neuroblastoma Research, Van Andel Research Institute, Grand Rapids, USA
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Laboratory for Translational Neuroblastoma Research, Van Andel Research Institute, Grand Rapids, USA
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Pediatric Oncology Translational Research Program, Helen DeVos Children’s Hospital, Grand Rapids, USA
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Michigan State University College of Medicine, Grand Rapids, USA
1 Laboratory for Translational Neuroblastoma Research, Van Andel Research Institute, Grand Rapids, USA
2 Laboratory for Translational Neuroblastoma Research, Van Andel Research Institute, Grand Rapids, USA
3 Laboratory for Translational Neuroblastoma Research, Van Andel Research Institute, Grand Rapids, USA
4 Laboratory for Translational Neuroblastoma Research, Van Andel Research Institute, Grand Rapids, USA
5 Laboratory for Translational Neuroblastoma Research, Van Andel Research Institute, Grand Rapids, USA
6 Pediatric Oncology Translational Research Program, Helen DeVos Children’s Hospital, Grand Rapids, USA
7 Michigan State University College of Medicine, Grand Rapids, USA
Background: Neuroblastoma exhibits a high incidence of chromosomal translocations, the most common being the gain of a portion of the long arm of chromosome 17. This region includes the gene BIRC5/survivin, which is highly upregulated in neuroblastoma and correlates with poor prognosis. Survivin is a member of the inhibitor of apoptosis family of proteins and is involved in tumor cell survival and migration. YM155 is a small molecule inhibitor of survivin transcription and has shown efficacy in several cancer model systems both in vitro and in vivo . Procedure: Cells were treated with YM155 and effects on migration, invasion, and apoptosis signaling were investigated in vitro . Tumor burden was assessed in xenografted mice by measuring tumor volume and liver metastases. Results: Treatment with YM155 caused a dose-dependent decrease in survivin expression and induction of apoptosis. Lower concentrations of YM155 reduced cell migration and invasion by 15% - 50% which varied by cell line. In a xenograft model, YM155 treatment inhibited tumor growth by 25% - 70%, reduced metastatic burden in the liver by 50%, and prolonged animal survival. Conclusion: The data suggest YM155 as a possible therapeutic agent for metastatic neuroblastoma.
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