Li Ji-Ping, Zhao Feng-Li, Yuan Ye, Sun Ting-Ting, Zhu Lei, Zhang Wen-You, Liu Mo-Xiang
Department of Pharmacology, Medical College, Yangzhou University, Yangzhou 225001, Jiangsu, China.
Department of Pharmacology, Medical College, Yangzhou University, Yangzhou 225001, Jiangsu, China.
Biochem Biophys Res Commun. 2017 Oct 21;492(3):391-396. doi: 10.1016/j.bbrc.2017.08.090. Epub 2017 Aug 26.
This study investigates the anti-angiogenic effect of 3β, 12β, 20(S)-trihydroxy dammarane-3-O-β-d-glucopyranosyl(1-2)-β-d-glucopyranoside(HRG), a new chemical compound obtained by structure modification on Ginseng saponins Rg3, associated with the regulation of matrix metalloproteinases(MMPs) and its upstream signal-regulated molecule of vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(b-FGF) in vitro, which plays an critical role in angiogenesis during the process of carcinoma. In our study, to investigate the anti-angiogenesis effect of HRG in HUVECs, we utilized cell proliferation assay, tube formation assay, wound-healing assay, Semi-quantitative reverse transcription PCR, and Western blot assay. Our results demonstrated that HRG plays a major role in the regulation of proliferation, migration and tube formation of HUVECs by suppressing the expression of VEGF and b-FGF in both transcriptional and post-transcriptional levels. In addition, the expression of MMP-2 and MMP-9, which were related to the ECM degradation, were down-regulated after administration of HRG as well. Overall, our results revealed that HRG strongly inhibited the process of angiogenesis and shows better effectiveness than Rg3.
本研究调查了3β,12β,20(S)-三羟基达玛烷-3-O-β-D-吡喃葡萄糖基(1-2)-β-D-吡喃葡萄糖苷(HRG)的抗血管生成作用。HRG是通过对人参皂苷Rg3进行结构修饰得到的一种新化合物,在体外与基质金属蛋白酶(MMPs)及其血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(b-FGF)的上游信号调节分子的调控相关,而这些分子在癌症发生过程中的血管生成中起关键作用。在我们的研究中,为了研究HRG对人脐静脉内皮细胞(HUVECs)的抗血管生成作用,我们采用了细胞增殖试验、管腔形成试验、伤口愈合试验、半定量逆转录聚合酶链反应(PCR)和蛋白质免疫印迹法(Western blot)。我们的结果表明,HRG通过在转录和转录后水平抑制VEGF和b-FGF的表达,在调节HUVECs的增殖、迁移和管腔形成中起主要作用。此外,与细胞外基质(ECM)降解相关的MMP-2和MMP-9的表达在给予HRG后也下调。总体而言,我们的结果表明,HRG强烈抑制血管生成过程,并且比Rg3显示出更好的效果。