Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases Extracellular Matrix-Associated Protein Expression
Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases Extracellular Matrix-Associated Protein Expression
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DOI：
10.1159/000493660
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Hsia, Shih-Min
中科院分区：
文献类型：
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作者：
Chen, Hsin-Yuan;Huang, Tsui-Chin;Hsia, Shih-Min
背景/目的：子宫肌瘤是一种良性子宫肿瘤，其最显著的病理生理特征是细胞外基质过度积聚。褐藻糖胶是一种从棕色海藻中提取的多糖，具有广泛的药理作用，包括抗纤维化作用。本实验旨在研究岩藻糖胶对转化生长因子-β(TGF-β)激活的ULS生长的影响。方法：采用ELT-3(Eker鼠子宫肌瘤来源细胞)和HUtSMC(人子宫平滑肌细胞)作为体外模型。用四甲基偶氮唑盐比色法测定细胞存活率。细胞集落形成用结晶紫染色。用流式细胞仪分析细胞边数、细胞周期和细胞凋亡率。免疫印迹分析检测蛋白质的表达。我们还进行了体内实验，以证实岩藻糖胶对裸鼠移植瘤的抑制作用。采用免疫组织化学方法对肿瘤组织进行检测。结果：在本研究中，岩藻糖胶在0.5 mg/ml剂量下可引起50%的细胞生长抑制，48h后干细胞活性下降，此外，岩藻糖胶还可诱导亚G1期细胞周期停滞和细胞凋亡。褐藻糖胶下调转化生长因子β3诱导的ELT-3细胞纤维连接蛋白、波形蛋白、α-SMA和COL1A1蛋白水平。在细胞机制上，岩藻糖胶可抑制转化生长因子β3诱导的p-Smad2和p-ERK1/2水平，以及β-连环蛋白移位到细胞核内。此外，岩藻糖胶还能抑制体内移植瘤的生长。结论：褐藻糖胶具有抗增殖、抗纤维化作用，对ULS的发生有保护作用。(C)2018年作者(S)由S.Karger AG，巴塞尔出版
Background/Aims: Uterine leiomyomas (ULs) are benign uterine tumors, and the most notable pathophysiologic feature of ULs is excessive accumulation of extracellular matrix (ECM). Fucoidan is a polysaccharide extracted from brown seaweeds that has a wide range of pharmacological properties, including anti-fibrotic effects. We aimed to study the effect of fucoidan on the growth of ULs activated by transforming growth factor beta (TGF beta). Methods: We used ELT-3 (Eker rat leiomyoma tumor-derived cells) and HUtSMC (human uterine smooth muscle cells) as in vitro models. Cell viability was determined by the MTT assay. Cell colony formation was stained using crystal violet. The side population, cell cycle and apoptosis were analyzed using flow cytometry. Protein expression was assayed by western blot analysis. We also conducted in vivo experiments to confirm the inhibitory effects of fucoidan in nude mouse xenograft models. Tumor tissues were assayed by immunohistochemistry analysis. Results: In our study, fucoidan caused a 50% growth inhibition using a dose of 0.5 mg/ml and decreased the stem cell activity after 48 h. In addition, fucoidan induced sub-G1 cell cycle arrest and apoptosis. Fucoidan down-regulated fibronectin, vimentin, alpha-SMA and the COL1A1 protein levels in TGF beta 3-induced ELT-3 cells. In the cellular mechanism, fucoidan abrogated TGF beta 3-induced levels of p-Smad2 and p-ERK1/2, as well as beta-catenin translocation into the nucleus. Furthermore, fucoidan suppressed xenograft tumor growth in vivo. Conclusion: Fucoidan displays anti-proliferation and anti-fibrotic effects and exerts protective effects against ULs development. (C) 2018 The Author(s) Published by S. Karger AG, Basel