論文 - 詳細
| RRC ID | 78686 |
|---|---|
| 著者 | Sawai T, Yamanegi K, Nishiura H, Futani H, Tachibana T. |
| タイトル | Sodium Valproate Enhances Semaphorin 3A-mediated Anti-angiogenesis and Tumor Growth Inhibition in Human Osteosarcoma Cells. |
| ジャーナル | Anticancer Res |
| Abstract |
BACKGROUND/AIM:Class 3 semaphorins, including semaphorin 3A (SEMA3A), are known endogenous angiogenesis inhibitors associated with endothelial cell migration and proliferation, and have been identified in many cancer cells. SEMA3A suppresses tumor angiogenesis by competing with VEGF, but tumors are known to have active angiogenesis, suggesting that expression of SEMA3A and its receptors is epigenetically restrained. To overcome this condition, we aimed to use histone deacetylase (HDAC) inhibitors to enhance the SEMA3A expression in osteosarcoma (OS) cells, thereby suppressing angiogenesis and inhibiting their proliferation and metastasis. MATERIALS AND METHODS:OS cell lines and human microvascular endothelial (HMVE) cells were treated with HDAC inhibitors such as sodium valproate (VPA) and Trichostatin A (TSA). Changes in the SEMA3A expression and its related receptors at the mRNA and protein levels, as well as the inhibitory effects on tumor angiogenesis, were investigated. RESULTS:VPA and TSA increased the expression of SEMA3A and its receptor NRP1, without inducing PLXNA1 in OS cells. Similarly, SEMA3A and NRP1 expression was increased in HMVE cells, but no growth inhibition was observed. Furthermore, SEMA3A induced by VPA in OS cell culture medium inhibited vascular tube formation of HMVE cells, and overexpression of SEMA3A enhanced OS cell growth inhibition. This growth-inhibitory effect of SEMA3A induced G1/S cell cycle arrest in OS cells. CONCLUSION:HDAC inhibitors have anti-angiogenic and anti-tumor activities that may be, in part, mediated via the SEMA3A/NRP1/PLXNA1 autocrine and paracrine pathways. |
| 巻・号 | 43(6) |
| ページ | 2539-2550 |
| 公開日 | 2023-6-1 |
| DOI | 10.21873/anticanres.16421 |
| PII | 43/6/2539 |
| PMID | 37247909 |
| MeSH | Bone Neoplasms* / drug therapy Histone Deacetylase Inhibitors / pharmacology Humans Neovascularization, Pathologic / metabolism Neuropilin-1 / genetics Osteosarcoma* / drug therapy Osteosarcoma* / genetics Osteosarcoma* / metabolism Semaphorin-3A / genetics Valproic Acid / pharmacology |
| リソース情報 | |
| ヒト・動物細胞 | Saos-2(RCB0428) |