Luan Yun-Yan, Liu Zi-Min, Zhong Jin-Yi, Yao Ru-Yong, Yu Hong-Sheng
Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, China E-mail :
Asian Pac J Cancer Prev. 2015;16(2):531-5. doi: 10.7314/apjcp.2015.16.2.531.
Vasculogenic mimicry (VM) refers to the unique ability of highly aggressive tumor cells to mimic the pattern of embryonic vasculogenesis, which was associated with invasion and metastasis. The grape seed proanthocyanidins (GSPs) had attracted much attention as a potential bioactive anti-carcinogenic agent. However, GSPs regulation of VM and its possible mechanisms in a triple-negative breast cancer cells (TNBCs) remain not clear. Therefore, we examined the effect of GSPs on VM information in HCC1937 cell model. In this study, we identified the VM structure via the three-dimensional (3D) matrix in vitro. Cell viability was measured using the CCK8 assay. The effects of GSPs on human triple-negative breast cancer cells (TNBCs) HCC1937 in terms of related proteins of VM information were determined using western blot analysis. In vitro, the tubular networks were found in highly invasive HCC1937 cells but not in the non-invasive MCF-7 cells when plated on matrigel. The number of vascular channels was significantly reduced when cells were exposed in GSPs (100 μg/ml) and GSPs (200 μg/ml) groups (all p<0.001). Furthermore, we found that treatment with GSPs promoted transition of the mesenchymal state to the epithelial state in HCC1937 cells as well as reducing the expression of Twist1 protein, a master EMT regulator.GSPs has the ability to inhibit VM information by the suppression of Twist1 protein that could be related to the reversal of epithelial-to-mesenchymal (EMT) process. It is firstly concluded that GSPs may be an potential anti-VM botanical agent for human TNBCs.
血管生成拟态（VM）是指高侵袭性肿瘤细胞模拟胚胎血管生成模式的独特能力，这与侵袭和转移相关。葡萄籽原花青素（GSPs）作为一种潜在的生物活性抗癌剂备受关注。然而，GSPs对三阴性乳腺癌细胞（TNBCs）中VM的调控及其可能机制仍不清楚。因此，我们在HCC1937细胞模型中研究了GSPs对VM形成的影响。在本研究中，我们通过体外三维（3D）基质鉴定VM结构。使用CCK8法检测细胞活力。通过蛋白质印迹分析确定GSPs对人三阴性乳腺癌细胞（TNBCs）HCC1937中VM相关蛋白的影响。在体外，当接种于基质胶上时，在高侵袭性的HCC1937细胞中发现了管状网络，而在非侵袭性的MCF-7细胞中未发现。当细胞暴露于GSPs（100μg/ml）和GSPs（200μg/ml）组时，血管通道数量显著减少（所有p<0.001）。此外，我们发现用GSPs处理可促进HCC1937细胞从间充质状态转变为上皮状态，并降低EMT主要调节因子Twist1蛋白的表达。GSPs能够通过抑制Twist1蛋白来抑制VM形成，这可能与上皮-间充质转化（EMT）过程的逆转有关。首次得出结论，GSPs可能是一种用于人类TNBCs的潜在抗VM植物制剂。
