Nagamine Takeaki, Hayakawa Kou, Kusakabe Takahiko, Takada Hisashi, Nakazato Kyoumi, Hisanaga Etsuko, Iha Masahiko
School of Health Science, Gunma University, 3-39-15 Showamachi, Maebashi, Gunma 371-8514, Japan.
Nutr Cancer. 2009;61(3):340-7. doi: 10.1080/01635580802567133.
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.
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。