Valproic acid inhibits angiogenesis in vitro and glioma angiogenesis in vivo in the brain.
Valproic acid inhibits angiogenesis in vitro and glioma angiogenesis in vivo in the brain.
复制标题
DOI：
10.2176/nmc.52.186
复制
发表时间：
2012-04
影响因子：
1.9
通讯作者：
S. Osuka;S. Takano;Shinya Watanabe;E. Ishikawa;Tetsuya Yamamoto;A. Matsumura
中科院分区：
文献类型：
--
作者：
S. Osuka;S. Takano;Shinya Watanabe;E. Ishikawa;Tetsuya Yamamoto;A. Matsumura
抗血管生成策略是治疗恶性胶质瘤的有效方法。组蛋白去乙酰化酶抑制剂（HDACIs）是具有抗血管生成作用的独特抗癌剂。本文研究了HDACIs、丙戊酸（VPA）在脑恶性胶质瘤中的体外和体内抗血管生成作用。在体外实验中，与胶质瘤细胞增殖相比，VPA在最佳浓度下以剂量依赖性方式优先抑制内皮细胞增殖。在常氧和低氧条件下，VPA以剂量依赖性方式减少胶质瘤细胞的血管内皮生长因子（VEGF）分泌。在血管生成试验中还发现VPA抑制管形成。在体内，VPA联合伊立替康治疗减少了脑肿瘤模型中表达因子VIII的血管数量。VPA通过直接（抑制内皮细胞增殖和管形成）和间接（减少胶质瘤细胞分泌VEGF）机制抑制胶质瘤血管生成。这些数据表明，VPA作为恶性胶质瘤患者的辅助治疗的潜在作用。
Antiangiogenic strategy is promising for malignant glioma. Histone deacetylase inhibitors (HDACIs) are unique anticancer agents that exhibit antiangiogenic effects. The in vitro and in vivo antiangiogenic effects of HDACIs, valproic acid (VPA), were investigated in malignant glioma in the brain. In vitro, VPA preferentially inhibited endothelial cell proliferation compared to glioma cell proliferation at the optimum concentration in a dose-dependent manner. VPA reduced vascular endothelial growth factor (VEGF) secretion of glioma cells in a dose-dependent manner under both normoxic and hypoxic conditions. VPA was also found to inhibit tube formation in the angiogenesis assay. In vivo, treatment with VPA combined with irinotecan reduced the number of vessels expressing factor VIII in the brain tumor model. VPA inhibits glioma angiogenesis by direct (inhibition of endothelial cell proliferation and tube formation) and indirect (decreased secretion of VEGF by glioma cells) mechanisms. These data suggest a potential role for VPA as an adjuvant therapy for patients with malignant glioma.