Study of specific gene expression in intractable childhood cancer and growth suppression and differentiation inducing effect of HDAC inhibitors

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10122
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Iehara Tomoko 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (20285266)
• Co-Investigator(Kenkyū-buntansha): 柳生 茂希 京都府立医科大学, 医学(系)研究科(研究院), 助教 (10572547) ; 細井 創 京都府立医科大学, 医学(系)研究科(研究院), 教授 (20238744) ; 菊地 顕 京都府立医科大学, 医学(系)研究科(研究院), 特任助教 (40453104) ; 宮地 充 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40584983)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 小児がん / HDAC阻害剤 / アポトーシス

Outline of Final Research Achievements

Introduction: We investigated whether the novel HDAC inhibitor YM753 has an antitumor effect on rhabdomyosarcoma and neuroblastoma in cell lines and in animal models.　Methods: The rhabdomyosarcoma and neuroblastoma cell lines were used. The antitumor effect and mechanism were examined. A xenograft mouse model was prepared to examine the antitumor effects. Results: This drug induced cell death in rhabdomyosarcoma and neuroblastoma cell lines. Induction of apoptosis was confirmed, showing G2/M phase arrest. The tumor cells showed G2/M phase arrest, confirming apoptosis induction. In addition, p21 expression induction, histone acetylation, and Cleaved caspase-3 induction were confirmed. In a mouse model, it suppressed tumor growth. In neuroblastoma it also induced differentiation. Discussion: From these results of culture experiments and animal experiments, it was effective as a novel therapeutic agent for rhabdomyosarcoma and neuroblastoma.

Free Research Field

小児がん

Academic Significance and Societal Importance of the Research Achievements

新規 HDAC 阻害剤 YM753 が、横紋筋肉腫、神経芽腫に対して、培養細胞および動物実験モデルで抗腫瘍効果を検討した。細胞株およびマウスモデルにおいては、腫瘍増殖を抑制した。神経芽腫では、分化も誘導した。これらの細胞培養実験、動物実験の結果から、横紋筋肉腫、神経芽腫の新規治療薬として有効であると考えられた。現在phase 1試験が米国で実施されていることから、小児がん領域での本薬剤の臨床応用が期待される。