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Inhibition of inducing multidrug resistance in human osteosarcoma cells by histone deacetylase inhibitor and DNA methylation inhibitor

Research Project

Project/Area Number 24592247
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionHyogo Medical University

Principal Investigator

TERADA NOBUYUKI  兵庫医科大学, 医学部, 名誉教授 (50150339)

Co-Investigator(Kenkyū-buntansha) NAKASHO Keiji  兵庫医科大学, 医学部, 教授 (00217712)
YAMANEGI Koji  兵庫医科大学, 医学部, 講師 (00434944)
YAMADA Naoko  兵庫医科大学, 医学部, 講師 (10319858)
HATA Masaki  兵庫医科大学, 医学部, 研究生(研究員) (10446057)
OHYAMA Hideki  兵庫医科大学, 医学部, 非常勤講師 (90280685)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords骨肉腫 / 薬剤耐性 / 非ステロイド系抗炎症剤
Outline of Final Research Achievements

We investigated that the combination of histone deacetylase (HDAC) inhibitor, hydralazine (DNA methylation inhibitor) and celecoxib (nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitor) inhibit inducing the expression of multidrug resistance (MDR) protein (MDR-1, MRP-1) in osteosarcoma cells without inhibiting cytotoxic sensitivity. The combination of HDAC inhibitor and celecoxib significantly inhibits cell-proliferation. This combination showed different reactions depending on the type of cells but generally inhibited. HDAC inhibitor alone increased MDR activity, however, combined with celecoxib reduced the activity depended on MDR-1 and MRP-1. These results suggest that combined treatment of HDAC inhibitor, hydralazine and celecoxib may be a useful for enhancing the effect of chemotherapy for osteosarcoma.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (10 results)

All 2015 2014 2013 2012 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (3 results)

  • [Journal Article] Sodium valproate, a histone deacetylase inhibitor, modulates the vascular endothelial growth inhibitor-mediated cell death in human osteosarcoma and vascular endothelial cells.2015

    • Author(s)
      Yamanegi K, Kawabe M, Futani H, Nishiura H, Yamada N, Kato-Kogoe N, Kishimoto H, Yoshiya S, Nakasho K.
    • Journal Title

      Int J Oncol

      Volume: 46 Issue: 5 Pages: 1994-2002

    • DOI

      10.3892/ijo.2015.2924

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of interleukin-34 and colony stimulating factor-1 in the stimulated periodontal ligament cells with tumor necrosis factor-α.2015

    • Author(s)
      Kawabe M, Ohyama H, Kato-Kogoe N, Yamada N, Yamanegi K, Nishiura H, Hirano H, Kishimoto H, Nakasho K.
    • Journal Title

      Med Mol Morphol.

      Volume: -

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Estrogen decreases the expression of claudin-5 in vascular endothelial cells in the murine uterus.2014

    • Author(s)
      Hata M, Yamanegi K, Yamada N, Ohyama H, Yukitatsu Y, Nakasho K, Okamura H, Terada N.
    • Journal Title

      Endocr J

      Volume: -

    • NAID

      130004443978

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Decreased expression of VE-cadherin and claudin-5 and increased phosphorylation of VE-cadherin in vascular endothelium in nasal polyps.2013

    • Author(s)
      Yukitatsu Y, Hata M, Yamanegi K, Yamada N, Ohyama H, Nakasho K, Kojima Y, Oka H, Tsuzuki K, Sakagami M, Terada N.
    • Journal Title

      Cell Tissue Res

      Volume: 352 Issue: 3 Pages: 647-657

    • DOI

      10.1007/s00441-013-1583-0

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hypoxia downregulates the expression of cell surface MICA without increasing soluble MICA in osteosarcoma cells in a HIF-1α-dependent manner.2012

    • Author(s)
      Yamada N, Yamanegi K, Ohyama H, Hata M, Nakasho K, Futani H, Okamura H, Terada N.
    • Journal Title

      Int J Oncol.

      Volume: 41(6) Issue: 6 Pages: 2005-2012

    • DOI

      10.3892/ijo.2012.1630

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Downregulation of matrix metalloproteinase-9 mRNA by valproic acid plays a role in inhibiting the shedding of MHC class I-related molecules A and B on the surface of human osteosarcoma cells.2012

    • Author(s)
      Yamanegi K, Yamane J, Kobayashi K, Ohyama H, Nakasho K, Yamada N, Hata M, Fukunaga S, Futani H, Okamura H, Terada N.
    • Journal Title

      Oncol Rep.

      Volume: 28(5) Issue: 5 Pages: 1585-1590

    • DOI

      10.3892/or.2012.1981

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Valproic acid cooperates with hydralazine to augment the susceptibility of human osteosarcoma2012

    • Author(s)
      Yamanegi K, Yamane J, Kobayashi K, Kato-Kogoe N, Ohyama H, Nakasho K, YamadaN, Hata M, Fukunaga S, Futani H, Okamura H, Terada N.
    • Journal Title

      cells to Fas- and NK cell-mediated cell death.Int J Oncol.

      Volume: 41(1) Pages: 83-91

    • DOI

      10.3892/ijo.2012.1438

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 骨肉腫細胞における低酸素誘導性の細胞表面MICAの発現低下2012

    • Author(s)
      山田 直子、山根木 康嗣、大山 秀樹、中正 恵二、秦 正樹、寺田 信行
    • Organizer
      日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒストン脱アセチル化阻害剤を用いた腫瘍血管新生抑制2012

    • Author(s)
      山根木康嗣、小林健太、中正恵二、大山秀樹、山田直子、秦正樹、寺田信行
    • Organizer
      日本病理学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 低酸素による細胞表面MICAの糖鎖修飾の低下

    • Author(s)
      山田直子, 山根木康嗣, 大山秀樹, 寺田信行, 中正恵二
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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