Development of novel sarcoma treatment guidelines targeting the sarcoma microenvironment

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09244
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Nippon Medical School (2023); Tokyo Medical and Dental University (2021-2022)
• Principal Investigator: Katsushi Kikuchi 日本医科大学, 大学院医学研究科, 研究生 (00602062)
• Co-Investigator(Kenkyū-buntansha): 佐藤 信吾 東京医科歯科大学, 医学部附属病院, 講師 (40462220) ; 麻生 義則 東京医科歯科大学, 大学院医歯学総合研究科, ジョイントリサーチ講座教授 (50345279)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: U2OS / osteosarcoma / PAI-1 / G2-M arrest

Outline of Final Research Achievements

Plasminogen activator inhibitor 1 (PAI-1) is highly expressed in the blood of patients with various malignant tumors or in the tumors themselves, and its expression is positively correlated with tumor grade. Therefore, PAI-1 is a potential target for cancer therapy. In this study, a small-molecule PAI-1 inhibitor, TM-5614, was tested on U2OS cells, which are osteosarcoma cell-like cells, to examine its effect on cell metabolism. The MTT assays and cell count analysis showed that TM5614 inhibited U2OS cell proliferation. We also tested the apoptotic activity of U2OS cells by multiple assays, and no induction of apoptosis by TM5614 was observed. In contrast, cell cycle analysis revealed that TM5614 induced U2OS cells in G2-M arrest. This study revealed that TM5614 treatment increased p53 and p21 Waf1/Cip1 expression in U2OS cells. In conclusion, we showed that the PAI-1 inhibitor TM5614 induced G2-M arrest in U2OS cells.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

我々は、PAI-1阻害剤TM5614がU2OS細胞のG2-M arrestを誘導することを示した。本研究の結果により、TM5614が骨肉腫治療の臨床転帰を改善する可能性が期待される。