Development of tumor-specific innovative drug Metformin for gastric cancer cell lines

• Project/Area Number: 15K10008
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Keio University
• Principal Investigator: Shigematsu Naoyuki 慶應義塾大学, 医学部(信濃町), 教授 (30178868)
• Co-Investigator(Kenkyū-buntansha): 深田 淳一 慶應義塾大学, 医学部(信濃町), 講師 (50338159) ; 川田 哲也 慶應義塾大学, 医学部(信濃町), 共同研究員 (60234077)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 放射線治療 / 放射線生物学 / 放射線増感剤 / 胃癌 / 放射線照射 / メトフォルミン

Outline of Final Research Achievements

Treatment results of gastric cancer in advanced stages need improvement. More effective anti-tumor radiosensitizing drug is anticipating. We selected metformin which is one of oral diabetes drugs as a promising radiosensitizer. Treatment effectiveness is assessed by irradiation, drug exposure alone and concomitant use of irradiation and drug in human gastric cell lines. Cell survival was evaluated with colony formation. Apoptosis and cell cycle distribution was evaluated using flow cytometric analyses. Combined therapy showed larger cytotoxic effect and higher apoptotic rate than the other exposure. The G2/G1 ratio was elevated and continued in 72-hours by combined therapy. Metformin showed not only cytotoxic effect but radiosensitizing effect in terms of arresting cell cycle in G2/M phase.

Research Products

• [Journal Article] Long-term Clinical Results of Concurrent Chemoradiotherapy for Patients with Cervical Esophageal Squamous Cell Carcinoma. (2017)
  • Author(s): Atsuhiro Kumabe, Sadatomo Zenda, Atsushi Motegi, Masakatsu Onozawa, Naoki Nakamura, Takashi Kojima, Hiroyuki Daiko, Naoyuki Shigematsu, and Tetsuo Akimoto
  • Journal Title: Anticancer Res Volume: 37(9) Issue: 9 Pages: 5039-5044
  • DOI: 10.21873/anticanres.11919
  • Peer Reviewed / Open Access
• [Journal Article] Long-term results of concurrent chemoradiotherapy with daily-low-dose continuous infusion of 5-fluorouracil and cisplatin (LDFP) for Stage I-II esophageal carcinoma (2017)
  • Author(s): Kumabe A、Fukada J、Kota R、Koike N、Shiraishi Y、Seki S、Yoshida K、Kitagawa Y、Shigematsu N
  • Journal Title: Diseases of the Esophagus Volume: 31 Issue: 4 Pages: 1-8
  • DOI: 10.1093/dote/dox138
  • Peer Reviewed
• [Presentation] ステージI-II期食道癌に対する化学放射線療法 (2017)
  • Author(s): 外山弘文、深田淳一、隈部篤寛、公田龍一、小池直義、白石悠、北川雄光、茂松直之
  • Organizer: 日本放射線腫瘍学会第30回学術大会
• [Presentation] Pleural and pericardial effusion after chemoradiotherapy in esophageal cancer patients. A predictive modeling using mean pericardial irradiated dose (2016)
  • Author(s): J. Fukada, T. Abe, A. Kumabe, H. Takaishi, Y. Kitagawa,N. Shigematsu
  • Organizer: 57th Annual Meeting of American Society for Therapeutic Radiology and Oncology
  • Place of Presentation: ボストン(アメリカ合衆国）
  • Year and Date: 2016-09-25
  • Int'l Joint Research
• [Presentation] PI3K/AKT/mTOR inhibitors enhance cytotoxic effect in combination with radiotherapy in gastric cancer cell lines (2015)
  • Author(s): 深田淳一, 公田龍一, 三島眞代, 川田哲也, 茂松直之
  • Organizer: 日本放射線腫瘍学会第28回学術大会
  • Place of Presentation: ベイシア文化ホール（群馬県前橋市）
  • Year and Date: 2015-11-19
• [Presentation] 食道癌化学放射線治療後の心嚢水・胸水貯留-平均心嚢照射線量を用いた予測モデル- (2015)
  • Author(s): 深田淳一，阿部貴行，隈部篤寛，高石官均，北川雄光，茂松直之
  • Organizer: 第53回癌治療学会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2015-10-29
• [Presentation] Cytogenetic Effects of Radiation and Caffeine on Normal Human Fibroblast and Ataxia Telangiectasia Heterozygous Fibroblast Cells (2015)
  • Author(s): Shigematsu N, Fukada J, Kota R, Shiraishi Y, Kawata T
  • Organizer: International congress of Radiation Research
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low-dose-rate Irradiation (2015)
  • Author(s): Kawata T, Liu C, Fukada J, Kota R, Shigematsu N
  • Organizer: International congress of Radiation Research
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] adiosensitization in gastric cancer cell lines using different PI3K/AKT/mTOR inhibitors (2015)
  • Author(s): Fukada J, Kota R, Mishima M, Kawata T, Shigematsu N
  • Organizer: International congress of Radiation Research
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2015-05-25
  • Int'l Joint Research