Marsdeniae tenacissimae extract (MTE) suppresses cell proliferation by attenuating VEGF/VEGFR2 interactions and promotes apoptosis through regulating PKC pathway in human umbilical vein endothelial cells
Marsdeniae tenacissimae extract (MTE) suppresses cell proliferation by attenuating VEGF/VEGFR2 interactions and promotes apoptosis through regulating PKC pathway in human umbilical vein endothelial cells
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Marsdeniae tenacissimae 提取物 (MTE) 通过减弱 VEGF/VEGFR2 相互作用来抑制细胞增殖，并通过调节人脐静脉内皮细胞中的 PKC 通路促进细胞凋亡
DOI：
10.1016/s1875-5364(17)30017-1
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发表时间：
2016-12-01
影响因子：
4.6
通讯作者：
Wang Zhen
中科院分区：
文献类型：
--
作者：
Chen Bing-Yu;Chen Dong;Wang Zhen
通关藤提取物（MTE），俗称“消癌平”，是一种具有抑制肿瘤细胞增殖、转移和促进肿瘤细胞凋亡作用的中药。然而，关于MTE对肿瘤血管生成的贡献及其潜在机制知之甚少。本研究旨在探讨MTE对人脐静脉内皮细胞（HUVECs）增殖和凋亡的影响及其分子机制。3-（4，5-二甲基噻唑-2-基）-5-（3-羧基甲氧基苯基）-2-（4-磺基苯基）-2H-四氮唑内盐（MTS）和PI染色流式细胞仪检测显示，MTE剂量依赖性地抑制HUVECs的增殖，使细胞周期阻滞于S期（P < 0.05）。Annexin V-FITC/PI染色流式细胞仪检测证实，MTE（160 μ L·mL（-1））可显著促进HUVECs凋亡（P < 0.001）。实时荧光定量RT-PCR和Western blot分析显示Bax表达增加，Bcl-2表达显著下降，caspase-3同时被激活，呈剂量依赖性（P < 0.05）。进一步的研究观察到血管内皮生长因子（VEGF）受体-2（VEGFR-2）、P2 Y 6受体（P2 Y 6 R）和趋化因子（C-C基序）配体2（CCL-2）的剂量依赖性下调，沿着PKC δ的激活和p53的上调，呈剂量依赖性（P < 0.05）。总之，本研究结果表明，MTE通过减弱CCL-2介导的VEGF/VEGFR 2相互作用抑制HUVECs增殖，并通过PKCd诱导的p53依赖性线粒体途径促进HUVECs凋亡，支持MTE可能被开发为一种有效的抗癌药物。
Marsdeniae tenacissimae extract (MTE), commonly known as Xiao-Ai-Ping in China, is a traditional Chinese herb medicine capable of inhibiting proliferation and metastasis and boosting apoptosis in various cancer cells. However, little is known about the contribution of MTE towards tumor angiogenesis and the underlying mechanism. The present study aimed to evaluate the effects of MTE on the proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) and the molecular mechanism. 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt (MTS) and PI-stained flow cytometry assays revealed that MTE dose-dependently reduced the proliferation of HUVECs by arresting cell cycle at S phase (P < 0.05). Annexin V-FITC/PI-stained flow cytometry confirmed that MTE (160 mu L.mL(-1)) enhanced the apoptosis of HUVECs significantly (P < 0.001). Real-time quantitative RT-PCR and Western blot analyses showed an increase in Bax expression and a sharply decline in Bcl-2 expression; caspase-3 was activated simultaneously in a dose-dependent manner (P < 0.05). Further study observed the dose-dependent down-regulation of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2), P2Y6 receptor (P2Y6R), and chemokine (C-C motif) ligand 2 (CCL-2), along with the activation of PKC delta and up-regulation of p53 in a dose-dependent manner in MTE-treated selected cells (P < 0.05). Collectively, the results from the present study suggested that MTE suppressed the proliferation by attenuating CCL-2-mediated VEGF/VEGFR2 interactions and promoted the apoptosis through PKCd-induced p53-dependent mitochondrial pathway in HUVECs, supporting that MTE may be developed as a potent anti-cancer medicine.