Exploration of novel anticancer activity via bioactive lipid mediators including resolvins E2/E3

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09459
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Hyogo Medical University
• Principal Investigator: Tsubamoto Hiroshi 兵庫医科大学, 医学部, 教授 (80340975)
• Co-Investigator(Kenkyū-buntansha): 上田 友子 兵庫医科大学, 医学部, 助教 (50793585) ; 井上 佳代 兵庫医科大学, 医学部, 非常勤講師 (80594754)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 腫瘍微小環境 / 腫瘍関連マクロファージ / 再分極

Outline of Final Research Achievements

A novel mechanism of action of itraconazole is the production of eicosapentaenoic acid-derived resolvins E2/E3. Inhibition of these metabolic pathways with ML351, a 12/15-LOX inhibitor, interfered with the action of itraconazole on CaSki cells. Suggesting an association with resolvin E2/E3-mediated TAM, M2 TAM was converted to M1 by itraconazole, and CaSki cell growth was suppressed in culture supernatants and co-cultures of M2 TAM after ITZ treatment. Single-cell analysis and three-color fluorescent immunostaining suggested that the mechanism of action was impaired lysosomal cholesterol transport.

Free Research Field

腫瘍微小環境

Academic Significance and Societal Importance of the Research Achievements

イトラコナゾールの作用機序がわかった。現在、ITZのターゲットの同定を試みている。TAM再分極を標的とした薬剤は臨床応用されておらず、同定されれば多癌種のTAMに対する新規治療薬開発が期待できる。