Arsenic trioxide sensitizes glioblastoma to a Myc inhibitor

HANDLE Open Access

Abstract

Glioblastoma multiforme (GBM) is associated with high mortality due to infiltrative growth and recurrence. Median survival of the patients is less than 15 months, increasing requirements for new therapies. We found that both arsenic trioxide and 10058F4, an inhibitor of Myc, induced differentiation of cancer stem-like cells (CSC) of GBM and that arsenic trioxide drastically enhanced the anti-proliferative effect of 10058F4 but not apoptotic effects. EGFR-driven genetically engineered GBM mouse model showed that this cooperative effect is higher in EGFRvIII-expressing INK4a/Arf-/- neural stem cells (NSCs) than in control wild type NSCs. In addition, treatment of GBM CSC xenografts with arsenic trioxide and 10058F4 resulted in significant decrease in tumor growth and increased differentiation with concomitant decrease of proneural and mesenchymal GBM CSCs in vivo. Our study was the first to evaluate arsenic trioxide and 10058F4 interaction in GBM CSC differentiation and to assess new opportunities for arsenic trioxide and 10058F4 combination as a promising approach for future differentiation therapy of GBM.

Journal

  • PLOS ONE

    PLOS ONE 10 (6), 2015-06-03

    Public Library of Science

Details 詳細情報について

  • CRID
    1050845760763095808
  • NII Article ID
    120005947136
  • ISSN
    19326203
  • HANDLE
    2433/214454
  • Text Lang
    en
  • Article Type
    journal article
  • Data Source
    • IRDB
    • CiNii Articles

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