New drug discovery against ovarian cancer focusing on the multifaceted effects of statins and their effects on the Warburg effect

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16780
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Keio University
• Principal Investigator: Kobayashi Yusuke 慶應義塾大学, 医学部(信濃町), 講師 (10439763)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: ドラッグリポジショニング / 卵巣癌 / スタチン / がん代謝

Outline of Final Research Achievements

From the perspective of drug repositioning to develop an already approved drug as a novel treatment for another disease, we conducted a basic study to apply a statin for dyslipidemia into the treatment of ovarian cancer. In addition to the mevalonate pathway, various biological processes, components, and molecular functions have been identified as pathways of action by statin. The expression of PTBP1, a regulatory factor, was significantly up-regulated in the statin-treated group. We established a system of the Histoculture Drug Response Assay to confirm the response of statin to human ovarian cancer specimens by collecting tumors from patients with ovarian cancer diagnosed by rapid intraoperative diagnosis.

Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

スタチンの抗腫瘍効果における多面的効果がメバロン酸経路以外の作用経路からも誘導されることを明らかにすることができた。加えて、スタチンががん細胞に特徴的なワールブルグ効果を酸化的リン酸化に誘導しうるのかという学術的問いに対して制御機構の一端を明らかとすることができた。また、Histoculture Drug Response Assay(HDRA)の系を樹立できたことで、ヒト卵巣癌検体にスタチンが奏効するかを明らかとすることができる。さらに、HDRAにおける増殖抑制率の結果から、奏効症例と非奏効症例に分類し、両群間の臨床病理学的背景を比較検討し有意に差のある因子を抽出することに繋げられる。