Sodium valproate and Rapamycin synergistically enhance the vascular endothelial growth inhibitor-mediated cell death in human osteosarcoma and vascular endothelial cells.
| Project/Area Number |
26462279
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山根木 康嗣 兵庫医科大学, 医学部, 講師 (00434944)
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| Co-Investigator(Renkei-kenkyūsha) |
TERADA Nobuyuki 兵庫医科大学, 医学部, 名誉教授 (50150339)
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| Research Collaborator |
KUMANISHI Shunsuke
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| 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 / 転移 / 悪性骨腫瘍 |
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| 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.
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Report
(5 results)
Research Products
(17 results)
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[Journal Article] Sodium valproate, a histone deacetylase inhibitor, modulates the vascular endothelial growth inhibitor-mediated cell death in human osteosarcoma and vascular endothelial cells.2015
Author(s)
Yamanegi K, Kawabe M, Futani H, Nishiura H, Yamada N, Kato-Kogoe N, Kishimoto H, Yoshiya S, Nakasho K.
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Journal Title
Int J Oncol
Volume: 46
Issue: 5
Pages: 1994-2002
DOI
Related Report
Peer Reviewed
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