Molecular Targeting Therapy Against Promyelocytic Leukemia Protein Using Arsenic Acids in Experimental Intracranial Medulloblastoma

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著者

    • GU Chunyu
    • Department of Neurosurgery, Hamamatsu University School of Medicine
    • YOKOTA Naoki
    • Department of Neurosurgery, Hamamatsu University School of Medicine
    • GAO Yun
    • Department of Neurosurgery, Hamamatsu University School of Medicine
    • AMANO Shinji
    • Department of Neurosurgery, Hamamatsu University School of Medicine
    • NAMBA Hiroki
    • Department of Neurosurgery, Hamamatsu University School of Medicine

抄録

Our previous study using human Daoy medulloblastoma cells showed that the promyelocytic leukemia (<i>PML</i>) gene was significantly upregulated (2.5-fold) in cells positive to prominin-1 antigen (CD133), a possible marker for cancer initiating cells. Arsenic trioxide (As<sub>2</sub>O<sub>3</sub>) is known to degrade PML protein and has been used for the treatment of patients with acute PML. In the present study, the effect of PML targeting therapy with As<sub>2</sub>O<sub>3</sub> and cytarabine (Ara-C) on Daoy medulloblastoma cell proliferation was investigated. Daoy cells were pretreated with As<sub>2</sub>O<sub>3</sub> for 6 weeks. The As<sub>2</sub>O<sub>3</sub>-pretreated Daoy cells were cultured in medium containing Ara-C and cell viability was examined. Next, the As<sub>2</sub>O<sub>3</sub>-pretreated Daoy cells were inoculated into the nude mouse brain and the effect of Ara-C on the tumor size was evaluated. A significant increase in chemosensitivity to Ara-C was observed in the As<sub>2</sub>O<sub>3</sub>-pretreated Daoy cells in both in vitro and in vivo conditions. PML and CCND1 (cyclin D1) protein expression of Daoy medulloblastoma cells was downregulated by As<sub>2</sub>O<sub>3</sub> treatment. PML has been proposed as a novel therapeutic target to eradicate quiescent leukemia-initiating cells, and PML-expressing CD133-positive cells are similarly a potential therapeutic target of treatment for medulloblastoma.<br>

収録刊行物

  • Neurologia medico-chirurgica = 神経外科

    Neurologia medico-chirurgica = 神経外科 52(2), 62-67, 2012-02-15

    一般社団法人 日本脳神経外科学会

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各種コード

  • NII論文ID(NAID)
    10030127244
  • NII書誌ID(NCID)
    AN00358613
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    04708105
  • データ提供元
    CJP書誌  J-STAGE 
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