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小百合块茎的皂苷单体 DT-13 通过多靶点活性抑制低氧和常氧条件下的血管生成。

The saponin monomer of dwarf lilyturf tuber, DT-13, inhibits angiogenesis under hypoxia and normoxia via multi-targeting activity.

机构信息

Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China.

出版信息

Oncol Rep. 2013 Apr;29(4):1379-86. doi: 10.3892/or.2013.2272. Epub 2013 Feb 5.

Abstract

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.

摘要

小百合块茎的皂苷单体 DT-13 通过减少缺氧下的人乳腺癌细胞黏附和迁移发挥抗癌活性。为了进一步研究 DT-13 的抗癌活性,我们研究了 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没有影响,但在常氧和缺氧条件下抑制管形成和迁移。此外,DT-13 显著减少了鸡胚尿囊膜模型中观察到的血管密度。Western blot 结果表明,DT-13 抑制了缺氧诱导的缺氧诱导因子 1α、p-细胞外信号调节激酶 1/2 和 p-Akt 的增加水平。酶联免疫吸附试验显示 DT-13 抑制了血管内皮生长因子诱导的迁移和管形成。此外,DT-13 降低了血管内皮生长因子诱导的 p-血管内皮生长因子受体 2 和 p-Akt 的水平。我们的数据表明,DT-13 抑制常氧和缺氧下的血管生成,并且还通过靶向多个靶点抑制血管内皮生长因子诱导的血管生成。

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