GSK-3β inhibition promotes cell death, apoptosis, and in vivo tumor growth delay in neuroblastoma Neuro-2A cell line

Amy Dickey, Stephen Schleicher, Kathleen Leahy, Rong Hu, Dennis Hallahan, Dinesh Kumar Thotala

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Neuroblastoma is the most common extracranial solid tumor of childhood. While survival rates are high for localized disease, treatment response remains poor for a subset of patients with large tumors or disseminated disease. Thus, there remains much room for improvement in treatment strategies for this disease. Using in vitro and in vivo systems, we present glycogen synthase kinase-3β (GSK-3β) inhibition as a potential mechanism to treat neuroblastoma. Using the specific GSK-3β inhibitor SB415286, we demonstrate that GSK-3β inhibition decreases the viability of Neuro-2A cells, as determined by cell proliferation assay and clonogenic survival. Moreover, we show that GSK-3β inhibition induces apoptosis in neuroblastoma cells, as determined by Annexin V staining and confirmed with DAPI staining. Using flow cytometry, we are able to demonstrate that SB415286 induces the accumulation of cells in the G2/M phase of the cell cycle. Finally, we show that these in vitro results translate into delayed tumor growth in vivo using a heterotopic tumor model in nude mice treated with SB415286. These findings suggest that GSK-3β is a potential molecular target for the treatment of neuroblastoma.

Original languageEnglish
Pages (from-to)145-153
Number of pages9
JournalJournal of Neuro-Oncology
Volume104
Issue number1
DOIs
StatePublished - Aug 2011

Keywords

  • Apoptosis
  • Cancer therapy
  • Glycogen synthase kinase-3 beta
  • Neuroblastoma

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