Development of a novel therapeutic drug for osteosarcoma using pristimerin

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10975
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kyoto 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
• 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

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.

Free Research Field

運動器機能再生外科(整形外科)

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。