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蒲公英多糖通过调节VEGF/HIF-1α表达对肝细胞癌发挥抗血管生成作用。

Dandelion Polysaccharide Exerts Anti-Angiogenesis Effect on Hepatocellular Carcinoma by Regulating VEGF/HIF-1α Expression.

作者信息

Ren Feng, Wu Kaixuan, Yang Yun, Yang Yingying, Wang Yuxia, Li Jian

机构信息

School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.

School of Nursing, Xinxiang Medical University, Xinxiang, China.

出版信息

Front Pharmacol. 2020 Apr 8;11:460. doi: 10.3389/fphar.2020.00460. eCollection 2020.

Abstract

Recent studies have revealed that natural plants-derived polysaccharides exhibit potent anti-tumor activity. Our earlier studies suggest that dandelion polysaccharide (DP) inhibits hepatocellular carcinoma (HCC) cell proliferation and . Here, we investigated the effects of DP on the angiogenesis of HCC and the potential molecular mechanisms by which DP regulates angiogenesis. Wound-healing and transwell invasion assays revealed that DP inhibited HUVECs migration and invasion , respectively. Tube formation assay, chick chorioallantoic membrane (CAM) assay, and immunohistochemistry (IHC) demonstrated that DP suppressed vasculogenesis and . Moreover, Western blot and immunofluorescence staining verified that DP treatment decreased the protein levels of some key factors involved in angiogenesis of HCC, such as hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), p-PI3K, and p-AKT. However, activation of PI3K/AKT pathway with insulin-like growth factor 1 (IGF-1) treatment attenuated the effect of DP on angiogenesis lowering the expression of HIF-1α and VEGF. In summary, we found that DP treatment inhibited angiogenesis and through suppressing expression of VEGF and HIF-1a. Furthermore, we showed that the expression of VEGF and HIF1-α was modulated by PI3K/AKT signaling. Collectively, our study suggests that DP is a promising anti-cancer drug candidate for treating HCC.

摘要

最近的研究表明,天然植物来源的多糖具有强大的抗肿瘤活性。我们早期的研究表明,蒲公英多糖(DP)可抑制肝癌(HCC)细胞增殖。在此,我们研究了DP对HCC血管生成的影响以及DP调节血管生成的潜在分子机制。伤口愈合和Transwell侵袭试验分别显示DP抑制了人脐静脉内皮细胞(HUVECs)的迁移和侵袭。管腔形成试验、鸡胚绒毛尿囊膜(CAM)试验和免疫组织化学(IHC)表明DP抑制了血管生成。此外,蛋白质印迹法和免疫荧光染色证实,DP处理降低了HCC血管生成中一些关键因子的蛋白质水平,如缺氧诱导因子1α(HIF-1α)、血管内皮生长因子(VEGF)、磷酸化磷脂酰肌醇-3激酶(p-PI3K)和磷酸化蛋白激酶B(p-AKT)。然而,用胰岛素样生长因子1(IGF-1)处理激活PI3K/AKT通路减弱了DP对血管生成的影响,降低了HIF-1α和VEGF的表达。总之,我们发现DP处理通过抑制VEGF和HIF-1α的表达来抑制血管生成。此外,我们表明VEGF和HIF1-α的表达受PI3K/AKT信号传导调节。我们的研究共同表明,DP是一种有前途的治疗HCC的抗癌候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f806/7158757/d28037fe9b63/fphar-11-00460-g001.jpg

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