Mode-of-action analysis of metformin to inhibit the epithelial mesenchymal transition and cancer stem cells in colon cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23889
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Hiroshima University
• Principal Investigator: Takakura Yuji 広島大学, 病院(医), 助教 (20581698)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 直腸癌

Outline of Final Research Achievements

We aimed to analyze the relationship between epithelial-mesenchymal transition (EMT), cancer stem cells (CSC) and chemoradiotherapy resistance in rectal cancer. We also evaluate the inhibition of metformin on EMT. Analysis of rectal cancer patients who received preoperative chemoradiotherapy, patients with CD44 highly-positive tumor showed significantly poor relapse-free survival in non-pCR patient group. We successfully generated the spheroid from colon cancer cell line, LoVo and DLD-1. Ratio of CD44+/CD133+ cells were increased in spheroid cells in compared with control cells.

Free Research Field

大腸外科

Academic Significance and Societal Importance of the Research Achievements

直腸癌は大腸癌の中でも治療成績が不良であり，局所再発率が高値であるため，いかに局所制御率を向上させるかが課題である．直腸癌に対する化学放射線治療は局所制御率を向上させる有効な治療法と認識されているものの，それでも局所再発率は依然10％程度にのぼる．化学放射線治療抵抗性への上皮間葉移行（EMT）及び癌幹細胞の関与を検討する今回の我々の検討では，臨床検体を用いた解析で大腸癌幹細胞のマーカーであるCD44高発現症例において有意に再発率が高値であった．直腸癌の治療抵抗性には大腸癌幹細胞が関与している可能性があり，さらなる研究成果が期待される．