化学修饰的茯苓β-D-葡聚糖结构与抗胃腺癌活性的关系

Correlation between structure and anti-gastric adenocarcinoma activity of β-D-glucan isolated from Poria cocos sclerotium

目的:探讨茯苓多糖及其衍生物的结构与抗胃腺癌活性之间的构效关系.方法:对从茯苓菌核中提取的(1→3)-?-D-葡聚糖PCS3-Ⅱ及其硫酸酯、羧甲基、羟乙基、羟丙基和甲基化衍生物,用粘度法、激光光散射(LLS)及尺寸排除色谱和光散射仪联用(SEC-LLS)表征了他们在磷酸缓冲液(PBS)中37℃下的[?]、Mw及<s2>z1/2等分子参数.然后用MTT法研究了PCS3-Ⅱ和几种衍生物对不同分化程度的胃腺癌细胞株MKN-45、SGC-7901和MKN-28生长的抑制作用.结果:S-PCS3-Ⅱ、C-PCS3-Ⅱ、M-PCS3-Ⅱ、HE-PCS3-Ⅱ和HP-PCS3-Ⅱ衍生物在PBS溶液中Mw值分别为3.8×104、18.9×104、16.0×104、76.8×104和224.3×104,未改性?-葡聚糖PCS3-Ⅱ几乎无抗胃腺癌活性,而他的硫酸酯和羧甲基衍生物对细胞株MKN-45、SGC-7901和MKN-28却显示较高的抑制率.结论:天然茯苓菌核多糖体外没有抗胃腺癌活性;水不溶性多糖PCS3-Ⅱ链上引入羧甲基和硫酸酯基后,其衍生物溶于水,且链刚性增大,同时其抗胃腺癌活性增强;良好的水溶性、较高的链刚性和适当大的分子量有利于茯苓多糖抗胃腺癌活性的提高.

AIM：To study the correlation between structure and anti-gastric adenocarcinoma activities of polysaccharides isolated from the sclerotiuma of Poria cocos and their derivatives.METHODS：A water insoluble（1 3）-β-D-glucan PCS3-Ⅱ isolated from fresh sclerotium of Poria cocos was sulfated,carboxymethylated,methylated,hydroxyethylated or hydroxypropylated to prepare five water-soluble derivatives,coded as S-PCS3-Ⅱ,C-PCS3-Ⅱ,M-PCS3-Ⅱ,HE-PCS3Ⅱ and HP-PCS3-Ⅱ.Their weight-average molecular mass（Mw）,intrinsic viscosity（[η]） and s2z1/2 were characterized by size exclusion chromatography（SEC） combined with laserlight scattering（LLS）,LLS,and viscometry.The antitumor activities of PCS3-Ⅱ and its derivatives were tested in vitro by MTT assay using gastric adenocarcinoma cell lines MKN-45,SGC-7901 and MKN-28.RESULTS：The Mw values of the derivatives S-PCS3-Ⅱ,C-PCS3-Ⅱ,M-PCS3-Ⅱ,HE-PCS3-Ⅱ and HP-PCS3-Ⅱ in PBS were determined to be 3.8×104,18.9×104,16.0×104,76.8×104,and 224.3 ×104,respectively.The native β-glucan did not show any anti-gastric adenocarcinoma activity,while the sulfated and carboxymethylated derivatives exhibited significant anti-gastric adenocarcinoma activity in MKN-45,SGC-7901 and MKN-28 cell lines.CONCLUSION：The polysaccharides from fresh sclerotium of Poria cocos showed no anti-gastric adenocarcinoma activity in vitro.The introduction of carboxymethylated and sulfated groups to water insoluble polysaccharide PCS3-Ⅱ increased their water-solubility,chain stiffness and anti-gastric adenocarcinoma activity.The sulfated derivatives showed obvious inhibitory e ects on gastric adenocarcinoma cells.