Applying Wnt/beta-catenin pathway inhibitors for the treatment of endometriosis

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K16774
• 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: Oita University
• Principal Investigator: Tomoko Hirakawa 大分大学, 医学部, 客員研究員 (20516132)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 子宮内膜症 / β-catenin / 線維化

Outline of Final Research Achievements

We investigated whether ICG-001 and C-82, which are inhibitors of CREB-binding protein (CBP) / β-catenin, could be therapeutic agents for endometriosis. For endometriotic stromal cells, the binding of β-catenin to CBP / P300 was confirmed by immunoprecipitation. Administration of ICG-001 and C-82 significantly suppressed collagen gel contraction and suppressed cicatrization. ICG-001 and C-82 suppressed cell proliferation, induced apoptosis, and suppressed cell migration. The expression of α-SMA involved in fibrosis was suppressed by administration of ICG-001 and C-82. ICG-001 reduced endometriotic lesions in model mice.

Free Research Field

子宮内膜症

Academic Significance and Societal Importance of the Research Achievements

子宮内膜症は生殖可能年齢女性において罹患頻度が高く、月経困難症や不妊の原因となる。また日本人に多いとされる卵巣明細胞癌の発生母地となることも知られている。本研究成果はCREB-binding protein (CBP) / β-catenin阻害剤であるICG-001とC-82が子宮内膜症治療の有望な選択肢であることを示した。女性のヘルスケアの観点からも、婦人科腫瘍の観点からも臨床的に応用可能な治療選択肢を示すことができた。