TITLE:
YM155 Inhibits Neuroblastoma Cell Migration and Survival in Vitro and Tumor Growth and Metastatic Burden in a Pre-Clinical Model
AUTHORS:
Heather M. Calderone, Akshita Dutta, Lauren Smith, Alexandra Eckardt, Ping Zhao, Giselle Saulnier Sholler
KEYWORDS:
Neuroblastoma, YM155, Survivin, Metastasis, Apoptosis
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.13,
November
26,
2014
ABSTRACT:
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 bothin vitroandin vivo. Procedure: Cells were treated with YM155 and effects on
migration, invasion, and apoptosis signaling were investigatedin 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.