| 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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| 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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