Antitumor efficacy of oncolytic reovirus against gastrointestinal tumor

• Project/Area Number: 15K09060
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nagoya City University
• Principal Investigator: Mori Yoshinori 名古屋市立大学, 大学院医学研究科, 研究員 (80468248)
• Co-Investigator(Kenkyū-buntansha): 片岡 洋望 名古屋市立大学, 大学院医学研究科, 准教授 (40381785) ; 青山 峰芳 名古屋市立大学, 大学院薬学研究科, 教授 (70363918)
• 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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: レオウイルス / 腫瘍溶解性ウイルス / 消化管腫瘍 / 消化管間葉系腫瘍 / Fas / GIST / reovirus

Outline of Final Research Achievements

We investigated whether reovirus has antitumor activity against GIST cells in the setting of imatinib sensitivity. Cell proliferation and apoptosis assays were performed using a human GIST cell line, GIST-T1, and imatinib-resistant GIST (GIST-IR) cells that we established. The molecular pathways responsible for cell damage by reovirus were explored using PCR-arrays and Western blots. Reovirus significantly induced apoptotic cell death in GIST-T1 and GIST-IR cells in vitro, despite differences in the activation of receptor tyrosine kinase pathways between GIST-T1 and GIST-IR. Molecular assays indicated the possibility that reovirus induces apoptotic cell death via Fas signaling. Furthermore, in vivo mouse tumor xenograft models demonstrated a significant anti-tumor effect of reovirus on both GIST-T1 and GIST-IR cells. Our results demonstrate the therapeutic potential of reovirus against GIST.

Research Products

• [Int'l Joint Research] University of Calgary/Dept Biochem & Molec Biol(カナダ)
• [Int'l Joint Research]
• [Journal Article] Anti-tumor efficacy of oncolytic reovirus against gastrointestinal stromal tumor cells. (2017)
  • Author(s): Inagaki Y, Kubota E, Mori Y, Aoyama M, Kataoka H, Johnston RN, Joh T.
  • Journal Title: Oncotarget Volume: 8(70) Issue: 70 Pages: 115632-115646
  • DOI: 10.18632/oncotarget.23361
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 消化管Gastrointestinal stromal tumor (GIST)に対する腫瘍崩壊ウイルス・レオウイルスの抗腫瘍効果の検討 (2017)
  • Author(s): 稲垣 佑祐、久保田英嗣、市川紘、野尻優、野村智史、林則之、西江裕忠、片野敬仁、尾関啓司、岡本泰幸、溝下勤、志村貴也、森義徳、谷田諭、片岡洋望、城卓志
  • Organizer: 第13回日本消化管学会総会学術集会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2017-02-17