The effects of metformin therapy on the suppression of gastroenterological cancer and identification of Metformin's target microRNA

• Project/Area Number: 15K18430
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor diagnostics
• Research Institution: Kagawa University
• Principal Investigator: KATO Kiyohito 香川大学, 医学部附属病院, 助教 (20596077)
• Research Collaborator: MASAKI Tsutomu ; IWAMA Hisakazu
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2016: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: Metformin / 消化器癌 / 膵臓癌 / 胆管癌 / 食道癌 / 癌抑制効果

Outline of Final Research Achievements

The goal of the present study was to evaluate the effects of metformin on human gastrointestinal cancer cell proliferation in vitro and in vivo, and to study microRNAs (miRNAs) associated with metformin anti-tumor effect in vitro and in vivo.Metformin inhibited the proliferation of cancer cells in vitro. Metformin blocked the cell cycle in G0/G1 in vitro and in vivo. This blockade was accompanied by a strong decrease of G1 cyclins, especially in cyclin D1, Cdk4, and Cdk6, and by a decrease in Rb, EGFR and IGF-1R phosphorylation in vitro and in vivo. The miRNA expression was markedly altered by the treatment with metformin in vitro and in vivo. Our results revealed that metformin inhibits human gastrointestinal cancer cell proliferation and tumor growth, possibly by suppressing the cellcycle-related molecules via alteration of miRNAs.

Research Products

• [Journal Article] The anti-diabetic drug metformin inhibits pancreatic cancer cell proliferation in vitro and in vivo: Study of the microRNAs associated with the antitumor effect of metformin. (2016)
  • Author(s): Kato K, Iwama H, Yamashita T, Kobayashi K, Fujihara S, Fujimori T, Kamada H, Kobara H, Masaki T.
  • Journal Title: Oncology Reports Volume: 35(3) Issue: 3 Pages: 1582-92
  • DOI: 10.3892/or.2015.4496
  • Peer Reviewed / Open Access
• [Journal Article] Antitumor effect of metformin on cholangiocarcinoma: In vitro and in vivo studies. (2015)
  • Author(s): Fujimori T, Kato K, Fujihara S, Iwama H, Yamashita T, Kobayashi K, Kamada H, Morishita A, Kobara H, Mori H, Okano K, Suzuki Y, Masaki T.
  • Journal Title: Oncology Reports Volume: 34(6) Issue: 6 Pages: 2987-96
  • DOI: 10.3892/or.2015.4284
  • Peer Reviewed
• [Presentation] Exhaustive analysis of microRNAs in the pancreatic cancer tissue obtained by endoscopic ultrasound-guided fine needle aspiration(EUS-FNA) (2016)
  • Author(s): 加藤清仁
  • Organizer: UEGW2016
  • Place of Presentation: オーストリア
  • Year and Date: 2016-10-17
  • Int'l Joint Research
• [Presentation] 抗糖尿病薬Metforminよる胆管癌細胞増殖の抑制機構 - MetforminのターゲットmicroRNAの同定 (2016)
  • Author(s): 藤森崇行
  • Organizer: 日本消化器病学会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2016-04-21
• [Presentation] THE ANTI-DIABETIC DRUG METFORMIN INHIBITS PANCREATIC CANCER CELL PROLIFERATION IN VITRO AND IN VIVO:STUDY OF MICRORNAS ASSOCIATED WITH THE ANTI-TUMOR EFFECT OF METFORMIN (2015)
  • Author(s): K.Kato
  • Organizer: 23rd United European Gastroenterology Week
  • Place of Presentation: スペイン、バルセロナ
  • Year and Date: 2015-10-15
  • Int'l Joint Research
• [Presentation] 抗糖尿病薬Metforminによる膵癌細胞増殖の抑制 - MetforminのターゲットmiRNAの同定 (2015)
  • Author(s): 加藤 清仁
  • Organizer: 日本膵臓学会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-06-19