The saponin monomer of dwarf lilyturf tuber, DT-13, inhibits angiogenesis under hypoxia and normoxia via multi-targeting activity.
The saponin monomer of dwarf lilyturf tuber, DT-13, inhibits angiogenesis under hypoxia and normoxia via multi-targeting activity.
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DOI：
10.3892/or.2013.2272
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发表时间：
2013-04
期刊：
影响因子：
4.2
通讯作者：
Ren-ping Zhao;Li Sun;Sen-sen Lin;X. Bai;Boyang Yu;S. Yuan;Luyong Zhang
中科院分区：
文献类型：
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作者：
Ren-ping Zhao;Li Sun;Sen-sen Lin;X. Bai;Boyang Yu;S. Yuan;Luyong Zhang
百合草的皂苷单体DT-13在低氧条件下通过减少人乳腺癌细胞的黏附和迁移而显示出抗癌活性。为了进一步研究DT-13的抗癌活性，我们考察了DT-13是否具有抗血管生成活性。DT-13对人脐静脉内皮细胞的增殖无影响，但在常氧和低氧条件下可抑制血管的形成和迁移。此外，从鸡绒毛膜尿囊膜模型观察到的体内血管密度，DT-13显著降低。Western blotting结果显示，DT-13可抑制缺氧诱导的缺氧诱导因子1α、p-细胞外信号调节蛋白1/2和p-Akt的表达。酶联免疫吸附试验显示DT-13可抑制血管内皮生长因子的分泌。DT-13在常氧和低氧条件下抑制血管内皮生长因子诱导的迁移和管状形成。此外，DT-13还可降低血管内皮细胞生长因子诱导的β-血管内皮生长因子受体2和p-Akt的水平。我们的研究结果表明，DT-13通过靶向多个元素抑制常氧和低氧条件下的血管生成，并抑制血管内皮生长因子诱导的血管生成。
The saponin monomer of dwarf lilyturf tuber, DT-13, exhibits anticancer activity by reducing human breast cancer cell adhesion and migration under hypoxia. To further investigate the anticancer activity of DT-13, we investigated whether DT-13 exhibits anti-angiogenic activity. DT-13 showed no effect on human umbilical vein endothelial cell proliferation but inhibited tube formation and migration under normoxia and hypoxia. Moreover, DT-13 significantly reduced density of vessels in vivo observed from a chicken chorioallantoic membrane model. Western blotting results showed that DT-13 suppressed the increased level of hypoxia-inducible factor 1α, p-extracellular signal-regulated kinase 1/2 and p-Akt induced by hypoxia. Enzyme-linked immunosorbent assay revealed that vascular endothelial growth factor excretion was suppressed by DT-13. DT-13 inhibited migration and tube formation induced by vascular endothelial growth factor under normoxia and hypoxia. In addition, DT-13 reduced the level of p-vascular endothelial growth factor receptor 2 and p-Akt induced by vascular endothelial growth factor. Our data suggest that DT-13 inhibits angiogenesis under normoxia and hypoxia and also inhibits angiogenesis induced by vascular endothelial growth factor via targeting at multi elements.