| RRC ID |
36922
|
| 著者 |
Yamanegi K, Kawabe M, Futani H, Nishiura H, Yamada N, Kato-Kogoe N, Kishimoto H, Yoshiya S, Nakasho K.
|
| タイトル |
Sodium valproate, a histone deacetylase inhibitor, modulates the vascular endothelial growth inhibitor-mediated cell death in human osteosarcoma and vascular endothelial cells.
|
| ジャーナル |
Int J Oncol
|
| Abstract |
The level of vascular endothelial growth inhibitor (VEGI) has been reported to be negatively associated with neovascularization in malignant tumors. The soluble form of VEGI is a potent anti-angiogenic factor due to its effects in inhibiting endothelial cell proliferation. This inhibition is mediated by death receptor 3 (DR3), which contains a death domain in its cytoplasmic tail capable of inducing apoptosis that can be subsequently blocked by decoy receptor 3 (DcR3). We investigated the effects of sodium valproate (VPA) and trichostatin A (TSA), histone deacetylase inhibitors, on the expression of VEGI and its related receptors in human osteosarcoma (OS) cell lines and human microvascular endothelial (HMVE) cells. Consequently, treatment with VPA and TSA increased the VEGI and DR3 expression levels without inducing DcR3 production in the OS cell lines. In contrast, the effect on the HMVE cells was limited, with no evidence of growth inhibition or an increase in the DR3 and DcR3 expression. However, VPA-induced soluble VEGI in the OS cell culture medium markedly inhibited the vascular tube formation of HMVE cells, while VEGI overexpression resulted in enhanced OS cell death. Taken together, the HDAC inhibitor has anti-angiogenesis and antitumor activities that mediate soluble VEGI/DR3-induced apoptosis via both autocrine and paracrine pathways. This study indicates that the HDAC inhibitor may be exploited as a therapeutic strategy modulating the soluble VEGI/DR3 pathway in osteosarcoma patients.
|
| 巻・号 |
46(5)
|
| ページ |
1994-2002
|
| 公開日 |
2015-5-1
|
| DOI |
10.3892/ijo.2015.2924
|
| PMID |
25778932
|
| MeSH |
Cell Line, Tumor
Endothelial Cells / metabolism
Endothelial Cells / pathology*
Enzyme-Linked Immunosorbent Assay
Histone Deacetylase Inhibitors / therapeutic use*
Humans
Hydroxamic Acids / therapeutic use
Osteosarcoma / metabolism
Osteosarcoma / pathology*
Real-Time Polymerase Chain Reaction
Receptors, Tumor Necrosis Factor, Member 6b / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Tumor Necrosis Factor Ligand Superfamily Member 15 / genetics
Tumor Necrosis Factor Ligand Superfamily Member 15 / immunology
Tumor Necrosis Factor Ligand Superfamily Member 15 / metabolism*
Valproic Acid / therapeutic use*
|
| IF |
3.899
|
| 引用数 |
9
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
Saos-2(RCB0428) |
