Antitumor efficacy of oncolytic reovirus against gastrointestinal tumor

2017 Fiscal Year Final Research Report

• 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
• Keywords: レオウイルス / 腫瘍溶解性ウイルス / 消化管腫瘍

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.

Free Research Field

消化管腫瘍