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Antiangiogenic effects of AG36, a triterpenoid saponin from Ardisia gigantifolia stapf.
Journal of Natural Medicines ( IF 2.5 ) Pub Date : 2020-07-08 , DOI: 10.1007/s11418-020-01427-4
Li-Hua Mu 1 , Li-Hua Wang 1 , Yu-Ning Wang 2 , Ping Liu 1 , Can Yan 3, 4
Affiliation  

AG36 is a triterpenoid saponin from Ardisia gigantifolia stapf. Our recent studies proved that AG36 displayed prominent cytotoxicity against breast cancer cells both in vitro and in vivo. However, whether AG36 has antiangiogenic properties is unknown. Therefore, in the present study, we evaluated the antiangiogenic effect of AG36 and the underlying mechanism. The results indicated that AG36 could significantly inhibit the proliferation, migration and invasion of human umbilical vein endothelial cells (HUVEC). Further antiangiogenic molecular mechanism investigation showed that AG36 significantly suppressed phosphorylated FAK and AKT, and downregulated the expressions of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) in HUVECs. PI3K inhibitor (LY294002) and FAK inhibitor (PF562271) pretreatment could markedly enhance AG36-induced inhibition of HUVEC proliferation and p-FAK suppression, respectively. In addition, AG36 inhibited the tumor growth in xenograft model and expressions of p–VEGFR2 and p–Akt in vivo. Molecular docking simulation indicated that AG36 formed hydrogen bonds and hydrophobic interactions within the ATP binding pocket of VEGFR2 kinase domain. The present study firstly revealed the high antiangiogenic potency and related underlying molecular of AG36, demonstrating that AG36 maybe a potential antiangiogenic cancer therapy agent or lead candidate.


中文翻译:

AG36是一种来自Ardisia gigantifolia stapf的三萜皂苷的抗血管生成作用。

AG36是来自Ardisia gigantifolia的三萜皂苷stapf。我们最近的研究证明,AG36在体外和体内均表现出对乳腺癌细胞的显着细胞毒性。但是,AG36是否具有抗血管生成特性尚不清楚。因此,在本研究中,我们评估了AG36的抗血管生成作用及其潜在机制。结果表明,AG36可显着抑制人脐静脉内皮细胞(HUVEC)的增殖,迁移和侵袭。进一步的抗血管生成分子机制研究表明,AG36显着抑制HUVECs中的磷酸化FAK和AKT,并下调血管内皮生长因子(VEGF)和血管内皮生长因子受体2(VEGFR2)的表达。PI3K抑制剂(LY294002)和FAK抑制剂(PF562271)预处理可以分别显着增强AG36诱导的HUVEC增殖抑制和p-FAK抑制。另外,AG36抑制异种移植模型中的肿瘤生长以及体内p–VEGFR2和p–Akt的表达。分子对接模拟表明AG36在VEGFR2激酶结构域的ATP结合口袋内形成氢键和疏水相互作用。本研究首先揭示了AG36的高抗血管生成潜能和相关的潜在分子,表明AG36可能是潜在的抗血管生成癌症治疗剂或主要候选药物。分子对接模拟表明AG36在VEGFR2激酶结构域的ATP结合口袋内形成氢键和疏水相互作用。本研究首先揭示了AG36的高抗血管生成潜能和相关的潜在分子,表明AG36可能是潜在的抗血管生成癌症治疗剂或主要候选药物。分子对接模拟表明AG36在VEGFR2激酶结构域的ATP结合口袋内形成氢键和疏水相互作用。本研究首先揭示了AG36的高抗血管生成潜能和相关的潜在分子,表明AG36可能是潜在的抗血管生成癌症治疗剂或主要候选药物。
更新日期:2020-07-08
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