茯苓β-D-葡聚糖衍生物结构与抗老年大鼠胃癌活性的关系

Relationship between structure of β-D-glucan derivatives from Poria cocos sclerotium and anti-gastric cancer activities of elderly rats

目的探讨茯苓多糖及其衍生物结构与抗老年大鼠胃癌活性之间的构效关系。方法从茯苓菌核中提取的（1—3）-β-D-葡聚糖（PCS3-II）及其硫酸酯、羧甲基、甲基化、羟乙基、羟丙基衍生物，观察PCS3-Ⅱ及5种衍生物在体内外对胃癌细胞株MKN-45、SGC-7901和MKN-28生长的抑制作用。结果未改性β-葡聚糖PCS3-Ⅱ几乎无抗胃癌活性，而PCS3-Ⅱ硫酸酯和羧甲基衍生物对细胞株MKN-45、SGC-7901、MKN-28有较高的抑制率；体内实验显示，硫酸酯和羧甲基衍生物对老年大鼠MKN-45胃癌移植瘤亦有较高抑制率，剂量为100mg／kg时对老年大鼠胃肿瘤的抑制率分别达到32．7％和36．4％。结论天然茯苓菌核多糖体外无抗胃癌活性；PCS3-Ⅱ羧甲基和硫酸酯基后衍生物溶于水，其抗胃癌活性增强；良好的水溶性、较高的链刚性和适当大的分子量有利于提高茯苓多糖抗老年人胃癌的活性。

Objective To study the correlation between structure of b-D -glucan derivatives from Poria cocos sclerotiuma and anti-gastric cancer activities of elderly rats. Methods A water insoluble （1-3）-β-D-glucan （PCS3-II ） isolated from fresh sclerotium of Poria cocos was sulfated, carboxymethylated, methylated, hydroxyethylated and hydroxypropylated, respectively, to prepare five water-soluble derivatives. Their activities of the native β-glucan and five derivatives against gastric cancer cell strains of MKN 45, SGC-7901and MKN-28 were tested in vitro and in vivo. Results The native β-glucan did not show any anti-gastric cancer activity, while the sulfated and carboxymethylated derivatives significantly exhibited the anti-gastric cancer activity against MKN-45, SGC-7901 and MKN-28 cells in vitro, and elderly rats with MKN-45 transplanted tumor , especially. The gastric cancer inhibition rates of elderly rats were 32.7% and 36.4% for the 100 mg/ kg sulfated and carboxymethylated derivatives, respectively. Conclusions The fresh sclerotium of Poria cocos polysaccharides can not show any anti-gastric cancer activity in vitro, but the sulfated and carboxymethylated derivatives may increase the inhibition effect. Water-solubility, higher chain stiffness and relatively molecular weight would be benefit to increase anti-elderly gastric cancer activity of polysaccbarides from Poria cocos sclerotiuma.