Radiosensitization in gastric cancer cell lines using different PI3K/AKT/mTOR inhibitors

• Project/Area Number: 24591850
• 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, 教授 (30178868)
• Co-Investigator(Kenkyū-buntansha): FUKADA Junichi 慶應義塾大学, 医学部, 講師 (50338159) ; NISHIMURA Shuichi 慶應義塾大学, 医学部, 助教 (40571138)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 放射線治療 / 放射線生物学 / 放射線増感剤 / 胃癌 / PI3K/Akt/mTOR経路

Outline of Final Research Achievements

Treatment of gastric cancer in advanced stages is still challenging. More effective anti-tumor radiosensitizing drug is desired to manage systemic disease. PI3K/AKT/ mTOR pathway is one of the important signal cascades which are activated by various growth factor receptors. We selected three PI3K/AKT/ mTOR pathway inhibitors. Treatment effectiveness is assessed by irradiation, drug exposure alone and combination of irradiation and drug in human gastric cell lines. Cell survival was evaluated with colony formation. Apoptosis was evaluated with flow cytometric analyses using AnnexinV-FITC/PI stain. Cell cycle distribution was evaluated using flow cytometric analyses. Concurrent exposure showed larger cytotoxic effect and higher apoptotic rate than the other exposure. The G2/G1 ratio was exclusively increased by concurrent exposure with irradiation and NVP-BEZ235 after 48-hours. NVP-BEZ235 seems to be a promising radiosensitizing drug in terms of arresting cell cycle in G2/M phase.

Research Products

• [Presentation] Radiosensitization in gastric cancer cell lines using different PI3K/AKT/mTOR inhibitors (2015)
  • Author(s): Junichi Fukada、Ryuichi Kota, Masayo Mishima, Tetsuya Kawata, Naoyuki Shigematsu
  • Organizer: International Congress of Radiation Reseach
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2015-05-25 – 2015-05-29
• [Presentation] 上腹部リンパ節の呼吸性移動－４ＤＣＴを用いた検討－ (2014)
  • Author(s): 祝田勇輝、深田淳一、酢谷真也、花田剛士、高橋常浩、北川雄光、茂松直之
  • Organizer: 日本放射線腫瘍学会第27回学術大会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2014-12-11 – 2014-12-13
• [Presentation] Symptomatic pericardial effusion after chemoradiation therapy for esophageal cancer: A historical comparison. (2013)
  • Author(s): Fukada J, Shigematsu N, Takeuchi H, Shiraishi Y, Hanada T, Ohashi T, Kota R, Kumabe A, Sutani S, Kitagawa Y.
  • Organizer: 55th Annual Meeting of American Society for Therapeutic Radiology and Oncology
  • Place of Presentation: Atlanta, GA, USA
• [Presentation] Inter- and intrafraction gastric motion study –Impact of breathing and stomach filling (2012)
  • Author(s): J. Fukada, N. Shigematsu, T. Hanada, T. Ohashi, T. Tanaka, Y. Shiraishi, H. Takeuchi, Y. Kitagawa
  • Organizer: American society for radiation oncology 54th annual meeting
  • Place of Presentation: Boston convention and exhibition center, Boston, MA, USA