Antitumor Effects of Metformin Due to Regulation of the Immunosuppressive Tumor Microenvironment

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10493
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kanazawa University
• Principal Investigator: Miyashita Tomoharu 金沢大学, 附属病院, 助教 (30397210)
• Co-Investigator(Kenkyū-buntansha): 太田 哲生 金沢大学, 医学系, 教授 (40194170)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 食道発癌 / 逆流性食道炎 / がん微小環境 / 化学予防

Outline of Final Research Achievements

Recently, metformin has been reported to be an anti-inflammatory, inhibition of phospho-Stat3 and antitumor activity. We evaluated that the dynamic alterations of infiltrating immune cells in esophageal carcinogenesis and investigated the anti-cancer effects of metformin.
Flow cytometric analysis demonstrated that the balance of M1- and M2-polarized macrophages, as well as the number of phospho-Stat3-positive macrophages, regulatory T cells, cytotoxic T cells, and natural killer cells, were dynamically changed at each stage of the disease. Metformin treatment stimulated immunomodulation at every stage. Overall, these findings suggest that metformin suppressed the esophageal carcinogenesis by improving the immunosuppressive tumor microenvironment.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

Ⅱ型糖尿病治療薬であるメトホルミンが癌組織を構築する抑制性免疫細胞の浸潤を抑制することにより癌微小環境を改変し、発癌抑制作用を有する可能性が示唆された。がん微小環境に対する既存薬再開発（ドラッグリポジショニング）につながる研究の成果と思われる。