水溶性高支化多糖及硫酸酯衍生物抗癌活性研究

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.

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

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.