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为探讨卡拉胶寡糖作为硫酸肝素类似物的抗肿瘤和抗血管新生机制,以宫颈肿瘤细胞HeLa和人脐静脉内皮细胞HUVEC为研究对象,考察几种不同聚合范围的寡糖结合bFGF及抑制乙酰肝素酶活性的作用。发现卡拉胶寡糖对正常细胞和肿瘤细胞均表现出低毒特征。在低浓度下,具有结合bFGF并能抑制bFGF引起的细胞增殖能力,其中λ-卡拉胶寡糖(聚合度2～8)效果最明显,在质量浓度为20μg.mL-1时,可达30%的抑制率。几种寡糖对乙酰肝素酶活性有不同趋势的抑制作用,在HeLa细胞中,λ-卡拉胶寡糖的抑制活性最高;在HUVEC细胞中,聚合度在9～17的κ-卡拉胶寡糖活性最高。结果表明,卡拉胶寡糖的类硫酸肝素生物活性与其分子量大小、硫酸取代量有明显的关系,低分子量、高硫酸基取代是其高活性的关键。
To investigate the antitumor and antiangiogenic mechanisms of carrageenan as an analogue of heparan sulfate, cervical cancer cells HeLa and human umbilical vein endothelial cells HUVEC were investigated to investigate the effect of different concentrations of oligosaccharides conjugated bFGF and inhibition of acetyl Heparinase activity. It was found that carrageenan oligosaccharides showed low toxicity to normal cells and tumor cells. At low concentration, it has the ability to bind bFGF and inhibit the proliferation of cells induced by bFGF. The effect of λ-carrageenan oligosaccharide (degree of polymerization 2 ~ 8) is the most obvious. When the concentration is 20μg.mL-1, % Inhibition rate. Several oligosaccharides have different inhibitory effects on heparanase activity. HeLa cells showed the highest inhibitory activity of λ-carrageenan oligosaccharide. In HUVEC cells, κ-carrageenan oligomers with 9-17 polymerization degree Sugar activity is highest. The results showed that the bioactivity of heparin sulfate of carrageenan oligosaccharides was significantly related to its molecular weight and the amount of sulfuric acid substitution. Low molecular weight and high sulfate groups were the key to its high activity.