Sodium valproate and Rapamycin synergistically enhance the vascular endothelial growth inhibitor-mediated cell death in human osteosarcoma and vascular endothelial cells.

2017 Fiscal Year Final Research Report

• Project/Area Number: 26462279
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Hyogo Medical University
• Principal Investigator: Futani Hiroyuki 兵庫医科大学, 医学部, 教授 (30248140)
• Co-Investigator(Kenkyū-buntansha): 山根木 康嗣 兵庫医科大学, 医学部, 講師 (00434944)
• Co-Investigator(Renkei-kenkyūsha): TERADA Nobuyuki 兵庫医科大学, 医学部, 名誉教授 (50150339)
• Research Collaborator: KUMANISHI Shunsuke
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 骨肉腫 / 腫瘍新生血管抑制 / ラパマイシン標的蛋白質阻害剤 / ヒストン脱アセチル化阻害剤 / 免疫療法

Outline of Final Research Achievements

We investigated the effects of anti-angiogenesis by Rapamycin (mTOR) in combination with valproic acid (VPA) on human osteosarcoma cells (OS). mTOR increased vascular endothelial growth inhibitor (VEGI) and a little effect of death receptor 3 (DR3) expression. However, in combination with VPA induced further increasing effect of both VEGI and DR3 without induction of decoy receptor 3 (DcR3) on OS and human microvascular endothelial cells (HMVE). Furthermore, combination of mTOR and VPA -induced soluble VEGI in the OS culture medium markedly inhibited the vascular tube formation of HMVE. These results suggest that mTOR and HDAC inhibitor has anti-angiogenesis and anti-tumor activities that mediate soluble VEGI/DR3-induced apoptosis via both autocrine and paracrine pathways. Finally, mTOR and VPA are considered to be one of the promising strategies in the development of novel anti-neovascularization therapy on osteosarcomas.

Free Research Field

整形外科