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

Research Project

Project/Area Number 19K23889
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0901:Oncology and related fields
Research InstitutionHiroshima University

Principal Investigator

Takakura Yuji  広島大学, 病院(医), 助教 (20581698)

Project Period (FY) 2019-08-30 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords直腸癌 / 化学放射線治療 / メトホルミン / CD44
Outline of Research at the Start

局所進行直腸癌に対する術前化学放射線治療は,術後の局所再発を低下させる有効な治療手段であるが,治療抵抗例,早期再発例も多く経験する.癌の治療抵抗性には,EMT(上皮間葉移行)が重要な意義を持つと考えられているが,近年EMTの誘導機序に放射線や癌幹細胞が関与しているという報告がある.また,糖尿病治療薬メトホルミンが癌幹細胞によるEMTを阻害する研究成果が報告されている.研究の概要は放射線誘導性EMTにおけるメトホルミンの抑制機序を解明し,直腸癌における化学放射線治療の効果を高める新たな治療戦略の構築を目指すことである.

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.

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.

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (3 results)

All 2021 2020

All Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] 直腸癌に対する術前CRTの治療成績2021

    • Author(s)
      望月哲矢,清水亘、高倉有二、河内雅年、田口和浩、赤羽慎太郎、佐藤幸毅、好中久晶、小野紘輔、松原啓壮、服部稔、大段秀樹
    • Organizer
      第94回大腸癌研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Pre- versus postoperative CAPOX plus bevacizumab (CAPOX-Bev) for resectable liver metastases from colorectal cancer (CLM): A randomized phase II/III trial (HiSCO-01).2020

    • Author(s)
      Yuji Takakura, Katsunori Shinozaki, Satoshi Ikeda, Hiroyuki Egi, Yuzo Hirata, Manabu Shimomura, Takafumi Oshiro, Takao Hinoi, Daisuke Sumitani, Masahiro Nakahara, Masanori Yoshimitsu, Naruhiko Honmyo, Tsuyoshi Kobayashi, Hideki Ohdan
    • Organizer
      2020 ASCO virtual scientific program
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The prognostic value of organ/space SSI in laparoscopic surgery for stage I colorectal cancer2020

    • Author(s)
      Shintaro Akabane, Yuji Takakura, Masatoshi Kochi, Kauzhiro Taguchi, Ikki Nakashima, Yusuke Sumi, Koki Sato, Hisaaki Yoshinaka, Minoru Hattori, Hiroyuki Egi, Hideki Ohdan
    • Organizer
      第33回日本内視鏡外科学会総会
    • Related Report
      2020 Annual Research Report

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Published: 2019-09-03   Modified: 2022-01-27  

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