卡拉胶寡糖与bFGF的结合活性及其对乙酰肝素酶活性的抑制作用  

Carrageenan oligosaccharides inhibit growth-factor binding and heparanase activity

作　　者：陈海敏[1] 高洋[1] 严小军[1] 

机构地区：[1]宁波大学海洋生物工程重点实验室,浙江宁波315211

出　　处：《药学学报》2011年第3期280-284,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30800860);浙江省自然科学基金资助项目(Y5100066);宁波市自然科学基金资助项目(2010A610028)

摘　　要：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。This study is designed to investigate the anti-tumor and anti-angiogenesis mechanism of carrageenan oligosaccharides.The effects of carrageenan oligosaccharides on basic fibroblast growth factor（bFGF） induced cell proliferation,heparanase activity and bFGF binding ability were evaluated in human cervical cancer cells（HeLa） and human umbilical vein endothelial cells（HUVEC）.Results indicate that,at rational concentrations,carrageenan oligosaccharides showed low cytotoxic effect.At relatively low concentrations（0.2-200 μg·mL-1）,these oligosaccharides could competitively bind bFGF and inhibit bFGF induced cell proliferation.In these samples,oligo-λ-carrageenans（dp2-8） were the most potent bFGF antagonists.At concentration of 20 μg·mL-1,their inhibitory ratio reached to 30%.The heparanase enzyme assay revealed that three kinds of carrageenan oligosaccharides showed different inhibitory activities to two cell lines.For HeLa cell,oligo-λ-carrageenans showed highest inhibitory effect,but for HUVEC,oligo-κ-carrageenans（dp9-17） were the best inhibitors.Current observations demonstrated that the biological activities of carrageenan oligosaccharides are closely related to the molecular weight,carbohydrate structure and the content and linking position of sulfur groups.Carrageenan oligosaccharides with high sulfate fraction,2-8 units saccharide size and suitable molecular structure are able to achieve potent heparin sulfate-like compounds.

关 键 词：卡拉胶寡糖 硫酸肝素 抑制剂 BFGF 乙酰肝素酶 

分 类 号：R963[医药卫生—微生物与生化药学]