Department of Cancer Preventive Material Development, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.
Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.
Int J Mol Sci. 2020 Jan 9;21(2):439. doi: 10.3390/ijms21020439.
Vasculogenic mimicry (VM) is the alternative process of forming vessel-like networks by aggressive tumor cells, and it has an important role in tumor survival, growth, and metastasis. Epigallocatechin-3-gallate (EGCG) is well known to have diverse bioactivities including anti-cancer effects. However, the efficacy of EGCG on VM is elusive. In this study, we explored whether and how EGCG affects VM in human prostate cancer (PCa) PC-3 cells. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Invasive and VM formation abilities were assessed by an invasion assay and a three-dimensional (3D) culture VM tube formation assay, respectively. Western blots were carried out. An immunofluorescence assay was performed to detect nuclear twist expression. EGCG effectively inhibited the invasive ability, as well as tubular channel formation, without affecting cell viability. EGCG significantly downregulated the expression of vascular endothelial cadherin (VE-cadherin) and its transcription factor, twist, N-cadherin, vimentin, phosphor-AKT, and AKT, but not phospho-erythropoietin-producing hepatocellular receptor A2 (EphA2) and EphA2. In addition, EGCG diminished the nuclear localization of twist. Treatment with SC79, an AKT activator, effectively rescued EGCG-inhibited VM formation. These results demonstrated for the first time that EGCG causes marked suppression of VM through inhibiting the twist/VE-cadherin/AKT pathway in human PCa PC-3 cells.
血管生成拟态（VM）是指侵袭性肿瘤细胞形成类似血管的网络的替代过程，它在肿瘤的存活、生长和转移中起着重要作用。表没食子儿茶素没食子酸酯（EGCG）具有多种生物活性，包括抗癌作用，这是众所周知的。然而，EGCG 对 VM 的疗效尚不清楚。在这项研究中，我们探讨了 EGCG 是否以及如何影响人前列腺癌（PCa）PC-3 细胞中的 VM。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定法测量细胞活力。通过侵袭测定和三维（3D）培养 VM 管形成测定分别评估侵袭和 VM 形成能力。进行了 Western blot 分析。进行了免疫荧光检测以检测核 twist 表达。EGCG 有效抑制了侵袭能力和管状通道形成，而不影响细胞活力。EGCG 显著下调了血管内皮钙黏蛋白（VE-cadherin）及其转录因子 twist、N-钙黏蛋白、波形蛋白、磷酸化 AKT 和 AKT 的表达，但不影响磷酸化红细胞生成素产生肝细胞受体 A2（EphA2）和 EphA2。此外，EGCG 减少了 twist 的核定位。用 AKT 激活剂 SC79 处理可有效挽救 EGCG 抑制的 VM 形成。这些结果首次表明，EGCG 通过抑制人类 PCa PC-3 细胞中的 twist/VE-cadherin/AKT 通路导致 VM 明显抑制。
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