水溶性高支化多糖及硫酸酯衍生物抗癌活性研究  

STUDIES ON ANTITUMOR ACTIVITY OF A WATER-SOLUBLE HYPERBRANCHED POLYSACCHARIDE AND ITS SULFATED DERIVATIVES

作　　者：陶咏真[1,2] 张俐娜[1] 韩露[3] 曾凡波[3] 丁侃[4] 

机构地区：[1]武汉大学化学与分子科学学院,武汉430072 [2]武汉科技学院新型纺织材料绿色加工及其功能化教育部重点实验室,武汉430073 [3]华中科技大学同济医学院药学系,武汉430030 [4]中国科学院上海药物研究所,上海201203

出　　处：《高分子学报》2009年第9期852-859,共8页Acta Polymerica Sinica

基　　金：国家自然科学基金重点项目(基金号30530850);面上项目(基金号20474048;20874079);国家高技术研究发展计划(863计划;项目号2006AA02Z102)资助项目

摘　　要：从虎奶菇菌核中提取出一种水溶性高支化葡聚糖,并用氯磺酸和吡啶在无水二甲亚砜中进行硫酸酯衍生化,制备出硫酸酯衍生物.用巴比赛小鼠动物实验研究该多糖及其硫酸酯衍生物的体内抗肉瘤S-180活性,以及用肝癌细胞株HepG2研究体外活性,同时讨论多糖分子尺寸与抗癌活性的关系.通过形态学、组织切片、以及酶联免疫法研究硫酸酯化对多糖抗肿瘤活性的影响.结果表明,支链多糖的均方根旋转半径在42.5-113 nm之间,显示出较高的体内和体外抗肿瘤活性,硫酸酯衍生物的均方根旋转半径在17.8-34.9 nm之间,抗癌活性随其分子尺寸的增大而逐渐提高.多糖及其硫酸酯衍生物能诱导人体肝癌HepG2细胞凋亡,且具有时间依赖性.它们对免疫反应的调节作用可通过肿瘤坏死因子TNF-α来介导.A water-soluble hyperbranchend β-glucan, extracted from sclerotia of Pleurotus tuber-regium was fractionated to obtain the fractions with different molecular weight. The polysaccharide fractions were treated with chlorosulfonic acid to synthesize sulfated derivatives. The antitumor activities of the water-soluble hyperbranched polysaccharide fractions and their sulfated derivatives were evaluated by in vivo test using SARCOMA 180 xenografted BALB/C mice, and in vitro measurement against HepG2 cell, respectively. The effect of introduction of sulfate groups in the polysaccharide on antitumor activities was compared with that of the native polysaccharides by morphological, histological and ELISA methods. The results indicated that the native polysaccharides, in the radius of gyration（ 〈S^2〉z^1/2 ） range from 42.5 nm to 113 nm, exhibited significantly inhibition impact on the xenografted tumor cell growth and antiproliferative activities against HepG2 cell in vitro. The antitumor activities of the sulfated derivatives increased progressively with the 〈S^2〉z^1/2 change from 17.8 nm to 34.9 nm. Mechanism study indicated that the native and sulfated glucans inhibited the proliferation of HepG2 cell through inducing the tumor cells apoptosis in a time dependent way. Immunological test demonstrated that both the native polysasaccharide and its sulfated derivatives using low dose （20 mg/kg） increased production of tumor necrosis factor alpha （TNF-α） in mouse plasma while the native one decreased amount of TNF-α using high does （60 mg/kg） with or without liopolysaccharide （LPS） stimulation.

关 键 词：高支化多糖 分子尺寸 链构象 硫酸酯化 抗肿瘤活性 

分 类 号：R151[医药卫生—营养与食品卫生学]