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岩藻依聚糖通过下调CXCL12对Huh7肝癌细胞的抑制作用。

Inhibitory effect of fucoidan on Huh7 hepatoma cells through downregulation of CXCL12.

作者信息

Nagamine Takeaki, Hayakawa Kou, Kusakabe Takahiko, Takada Hisashi, Nakazato Kyoumi, Hisanaga Etsuko, Iha Masahiko

机构信息

School of Health Science, Gunma University, 3-39-15 Showamachi, Maebashi, Gunma 371-8514, Japan.

出版信息

Nutr Cancer. 2009;61(3):340-7. doi: 10.1080/01635580802567133.

Abstract

The aim of this study is to assess whether fucoidan modulates the expression of chemokine ligand 12 (CXCL12)/chemokine receptor 4 (CXCR4) and exerts antitumor activity toward Huh7 hepatoma cells. According to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, fucoidan inhibited the growth of Huh7 cells and HepG2 cells in a dose-dependent manner, with a 50% inhibition of cell growth (IC50) of 2.0 and 4.0 mg/ml, respectively. alpha-fetoprotein levels in medium collected from fucoidan-treated cells were significantly decreased in Huh7 cells but not in HepG2 cells. Western blotting revealed that the amount of alpha-fetoprotein was decreased by 1.0 mg/ml of fucoidan in Huh7 cells, whereas it was unchanged in HepG2 cells. In Huh7 cells, CXCL12 mRNA expression was significantly downregulated by 1.0 mg/ml of fucoidan, whereas CXCR4 mRNA expression was unchanged by fucoidan. CXCL12 and CXCR4 mRNA were barely expressed in HepG2 cells. In addition, 1.0 mg/ml of fucoidan mildly arrested the cell cycle and induced apoptosis in Huh7 cells. The findings suggest that fucoidan exhibits antitumor activity toward Huh7 cells through the downregulation of CXCL12 expression.

摘要

本研究的目的是评估岩藻依聚糖是否调节趋化因子配体12(CXCL12)/趋化因子受体4(CXCR4)的表达,并对Huh7肝癌细胞发挥抗肿瘤活性。根据3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)分析,岩藻依聚糖以剂量依赖方式抑制Huh7细胞和HepG2细胞的生长,对细胞生长的50%抑制(IC50)分别为2.0和4.0mg/ml。从经岩藻依聚糖处理的细胞收集的培养基中的甲胎蛋白水平在Huh7细胞中显著降低,但在HepG2细胞中未降低。蛋白质免疫印迹法显示,1.0mg/ml岩藻依聚糖使Huh7细胞中甲胎蛋白量减少,而在HepG2细胞中则无变化。在Huh7细胞中,1.0mg/ml岩藻依聚糖显著下调CXCL12 mRNA表达,而岩藻依聚糖对CXCR4 mRNA表达无影响。CXCL12和CXCR4 mRNA在HepG2细胞中几乎不表达。此外,1.0mg/ml岩藻依聚糖使Huh7细胞的细胞周期轻度停滞并诱导其凋亡。这些发现表明,岩藻依聚糖通过下调CXCL12表达对Huh7细胞表现出抗肿瘤活性。

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