Echinacoside (ECH) suppresses proliferation, migration, and invasion of human glioblastoma cells by inhibiting Skp2-triggered epithelial-mesenchymal transition (EMT)
Echinacoside (ECH) suppresses proliferation, migration, and invasion of human glioblastoma cells by inhibiting Skp2-triggered epithelial-mesenchymal transition (EMT)
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Echinacoside (ECH) 通过抑制 Skp2 触发的上皮间质转化 (EMT) 来抑制人胶质母细胞瘤细胞的增殖、迁移和侵袭
DOI：
10.1016/j.ejphar.2022.175176
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发表时间：
2022
影响因子：
5
通讯作者：
Zhaotao Wang
中科院分区：
文献类型：
--
作者：
Shengying Shi;Yixin Qin;Danmin Chen;Yanhong Deng;Jinjin Yin;Shaozhi Liu;Hang Yu;Hanhui Huang;Chaoduan Chen;Yinyue Wu;Duan Zou;Zhaotao Wang
松果菊苷（ECH）是从盐生肉苁蓉（Cistanches salsa）的茎中提取的苯乙醇类化合物，一种用于中药制剂的草药，并且对多形性胶质母细胞瘤（GBM）有效。上皮间质转化（EMT）是肿瘤发生和转移的基础，并增加GBM细胞的恶性行为。S期激酶相关蛋白2（skp 2）是一种与EMT相关的癌蛋白，在GBM中高表达，与肿瘤的耐药性、分级和预后密切相关。本研究采用CCK-8、EdU掺入、transwell、集落形成和球体形成等方法，观察ECH对体外培养的GBM细胞活力、增殖、迁移和侵袭能力的影响，探讨ECH对GBM细胞生长和skp 2诱导的EMT的抑制作用。使用U87异种移植模型检查ECH的体内抗胶质瘤作用。免疫荧光染色和Western blotting检测skp 2蛋白、EMT相关标志物（vimentin和snail）和干性标志物（Nestin和sox 2）的表达水平，结果表明ECH能抑制GBM细胞的增殖、侵袭和迁移，抑制U87移植瘤的生长。此外，ECH下调skp 2蛋白，EMT相关标志物（波形蛋白和蜗牛）和干性标志物（sox 2和巢蛋白）。ECH对skp 2基因敲除的GBM细胞的抑制作用增强，而对skp 2基因异位表达的GBM细胞的抑制作用则相反。ECH通过抑制skp 2诱导的GBM细胞EMT而抑制胶质瘤的发生。
Echinacoside (ECH) is a phenylethanoid extracted from the stems of Cistanches salsa, an herb used in Chinese medicine formulations, and is effective against glioblastoma multiforme (GBM). Epithelial-mesenchymal transition (EMT) is the cornerstone of tumorigenesis and metastasis, and increases the malignant behavior of GBM cells. The S phase kinase-related protein 2 (skp2), an oncoprotein associated with EMT, is highly expressed in GBM and significantly associated with drug resistance, tumor grade and dismal prognosis. The aim of this study was to explore the inhibitory effects of ECH against GBM development and skp2-induced EMT.CCK-8, EdU incorporation, transwell, colony formation and sphere formation assays were used to determine the effects of ECH on GBM cell viability, proliferation, migration and invasion in vitro. The in vivo anti-glioma effects of ECH were examined using a U87 xenograft model. The expression levels of skp2 protein, EMT-associated markers (vimentin and snail) and stemness markers (Nestin and sox2) were analyzed by immunofluorescence staining and western blotting experiments.ECH suppressed the proliferation, invasiveness and migration of GBM cells in vitro, as well as the growth of U87 xenograft in vivo. In addition, ECH downregulated the skp2 protein, EMT-related markers (vimentin and snail) and stemness markers (sox2 and Nestin). The inhibitory effects of ECH were augmented in the skp2-knockdown GBM cells, and reversed in cells with ectopic expression of skp2.ECH inhibits glioma development by suppressing skp2-induced EMT of GBM cells.