A novel exopolysaccharide EPS364 from Vibrio alginolyticus inhibit cancer cell growth via blocking cell adhesion

The prognosis of liver cancer was inferior among tumors. New medicine treatments are urgently needed. In this study, a novel exopolysaccharide EPS364 was purified from Vibrio alginolyticus 364 which was isolated from South China Sea cold seep. Further research suggested that EPS364 consisted of mannose, glucosamine, gluconic acid, galactosamine, arabinose with a molar ratio of 5:9:3.4:0.8:1.5. The molecular weight of EPS364 was 14.8 kDa. Our results further indicated that EPS364 was β-linked and phosphorylated polysaccharide. Notably, EPS364 exhibited significant anti-tumor activity. Besides, EPS364 induced Huh7.5 cells apoptosis, collapse of mitochondrial membrane potential (MMP) and generation of reactive oxygen species (ROS). Proteomic and quantitative real-time PCR analyses indicated that EPS364 blocked cancer cell adhesion and induced apoptosis via targeting FGF19–FGFR4 signaling pathway. These findings suggested that EPS364 was a promising anti-tumor agent for pharmacotherapy.

相较于其他肿瘤，肝癌的预后效果更差，亟需研发新型治疗药物。本研究从分离自南海冷泉的溶藻弧菌（Vibrio alginolyticus）364菌株中纯化得到一种新型胞外多糖（exopolysaccharide，EPS）EPS364。经分析，EPS364由甘露糖、葡萄糖胺、葡萄糖酸、半乳糖胺与阿拉伯糖按照摩尔比5:9:3.4:0.8:1.5组成，其分子量为14.8 kDa。实验结果进一步证实，EPS364为β-糖苷键连接的磷酸化多糖。值得注意的是，EPS364展现出显著的抗肿瘤活性。此外，EPS364可诱导Huh7.5肝癌细胞发生凋亡，引发线粒体膜电位（mitochondrial membrane potential，MMP）崩溃，并产生活性氧（reactive oxygen species，ROS）。蛋白质组学与实时荧光定量PCR分析结果显示，EPS364可通过靶向FGF19–FGFR4信号通路，抑制癌细胞黏附并诱导其凋亡。上述研究结果表明，EPS364是一种极具开发潜力的抗肿瘤治疗候选药物。