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Development of a novel therapeutic drug for osteosarcoma using pristimerin

Research Project

Project/Area Number 17K10975
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Terauchi Ryu  京都府立医科大学, 医学(系)研究科(研究院), 講師 (20575154)

Co-Investigator(Kenkyū-buntansha) 白井 寿治  京都府立医科大学, 医学(系)研究科(研究院), 准教授 (20397186)
新井 祐志  京都府立医科大学, 医学(系)研究科(研究院), 准教授 (50347449)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsプリスチメリン / アポトーシス / 骨肉腫 / 細胞増殖抑制効果 / テルペノイド / 天然有機化合物 / カスパーゼ / 天然化合物
Outline of Final Research Achievements

There are very few treatments for musculoskeletal tumors, compared to other cancers; thus, novel therapeutic drugs are needed. Pristimerin (PM) reportedly has antitumor effects on various cancers, such as of the breast and prostate. The purpose of this study was to evaluate the antitumor effects of PM on human osteosarcoma cells. Treatment of the human osteosarcoma cell lines, MNNG and 143B, with PM led to a dose-dependent decrease in cell viability. The effects of PM on apoptosis were evaluated with the Annexin V/propidium iodide assay and analysis of caspases 3, 8, and 9 activities. Western blot analysis showed that PM caused a decrease in the expression of Akt, mTOR, and NF-κB. The volumes and weights of human osteosarcoma xenografts decreased significantly with PM treatment. The results of this study revealed that PM can inhibit human osteosarcoma growth in vitro and in vivo, and may be a novel therapeutic agent for the disease.

Academic Significance and Societal Importance of the Research Achievements

本研究では、プリスチメリン(以下、PM)の抗腫瘍効果の検討を、in vitroおよびin vivoで行った。In vitroで、PMは肉腫細胞に対しては濃度依存性に抗腫瘍効果を認め、正常細胞における影響は低値であった。また、in vivoにおいても、抗腫瘍効果を認めつつ、マウスの体重や肝機能へは明らかな影響を及ぼさなかった。このことから、PMは低濃度で十分な抗腫瘍効果を有し、なおかつ副作用の少ない理想的な薬剤であると考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (9 results)

All 2019 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Antitumor effects of pristimerin on human osteosarcoma cells in vitro and in vivo.2017

    • Author(s)
      Mori Y, Shirai T, Terauchi R, Tsuchida S, Mizoshiri N, Hayashi D,
    • Journal Title

      OncoTargets and Therapy

      Volume: 10 Pages: 5703-5710

    • DOI

      10.2147/ott.s150071

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Efficacy of pristimerin for soft tissue sarcoma in vitro and in vivo study2019

    • Author(s)
      林 大智
    • Organizer
      2019 Annual Meeting of Orthopaedic Research Society
    • Related Report
      2019 Annual Research Report
  • [Presentation] 軟部肉腫に対する天然有機化合物プリスチメリンの効果2019

    • Author(s)
      林 大智
    • Organizer
      第52回日本整形外科学会骨・軟部腫瘍学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒト線維肉腫細胞に対するプリスチメリンの抗腫瘍効果の検討2019

    • Author(s)
      林 大智
    • Organizer
      第34回日本整形外科学会基礎学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Efficacy of pristimerin for soft tissue sarcoma in vitro and in vivo study2019

    • Author(s)
      Daichi Hayashi, Toshiharu Shirai, Ryu Terauchi, Shinji Tsuchida, Naoki Mizoshiri, Yuki Mori, Yuji Arai, Osam Mazda, Toshikazu Kubo
    • Organizer
      ORS 2019 Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 天然有機化合物であるプリスチメリンの骨肉腫細胞に対する抗腫瘍効果2018

    • Author(s)
      林 大智,白井寿治,寺内 竜,土田真嗣,溝尻直毅, 森 裕貴,勝山祐誠,新井祐志,松田 修,久保俊一
    • Organizer
      日本整形外科学会骨・軟部腫瘍学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 天然有機化合物であるプリスチメリンの線維肉腫細胞に対する抗腫瘍効果2018

    • Author(s)
      林 大智,白井寿治,寺内 竜,土田真嗣,溝尻直毅,森 裕貴,勝山祐誠,新井祐志,松田 修,久保俊一
    • Organizer
      日本整形外科学会基礎学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Antitumor effects of pristimerin on human osteosarcoma cells in vitro and in vivo2018

    • Author(s)
      Mori Y, Shirai T,Terauchi R, Tsuchida S, Mizoshiri N,Hayashi D, Yuji A, Mazda O, Kubo T
    • Organizer
      ORS 2018 Annual Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 天然有機化合物であるプリスチメリンの骨肉腫細胞株に対する抗腫瘍効果の検討2017

    • Author(s)
      森 裕貴,白井寿治,寺内 竜,土田真嗣,溝尻直毅,新井祐志,松田 修,久保俊一
    • Organizer
      第32回 日本整形外科学会基礎学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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