岩藻依聚糖通过下调人淋巴管内皮细胞中VEGFR3和PROX1的表达来抑制淋巴管生成。

Fucoidan inhibits lymphangiogenesis by downregulating the expression of VEGFR3 and PROX1 in human lymphatic endothelial cells.

作者信息

Yang Yazong, Gao Zixiang, Ma Yanhong, Teng Hongming, Liu Zundong, Wei Hengyun, Lu Yanbing, Cheng Xiaofang, Hou Lin, Zou Xiangyang

机构信息

Department of Biotechnology, Dalian Medical University, Dalian, 116044, China.

College of Life Sciences, Liaoning Normal University, Dalian, 116081, China.

出版信息

Oncotarget. 2016 Jun 21;7(25):38025-38035. doi: 10.18632/oncotarget.9443.

Lymphangiogenesis is one of the promoters of tumor lymphatic metastasis. Fucoidan which is a fucose-enriched sulfated polysaccharide has effect on various pharmacological activities including anti-metastasis activity. However, the inhibitory effect of fucoidan on lymphangiogenesis remains unclear. Here, fucoidan extracted from U. pinnatifida sporophylls suppressed HLECs proliferation, migration and tube-like structure formation, and had inhibitory effect of tumor-induced lymphangiogenesis in vitro. Additionally, we found that fucoidan had a dose-dependent depressive effect on the expressions of PROX1, vascular endothelial growth factor receptor 3 (VEGFR3), NF-κB, phospho-PI3K and phospho-Akt in HLECs. Moreover, anti-lymphangiogenesis effect of fucoidan was assessed by using mouse tumor model. In summary, fucoidan inhibit tumor lymphangiogenesis and lymphatic metastasis by suppressing the NF-κB/PI3K/Akt signaling pathway through reduced levels of PROX1 and VEGFR3.

淋巴管生成是肿瘤淋巴转移的促进因素之一。岩藻依聚糖是一种富含岩藻糖的硫酸化多糖，具有多种药理活性，包括抗转移活性。然而，岩藻依聚糖对淋巴管生成的抑制作用仍不清楚。在此，从裙带菜孢子叶中提取的岩藻依聚糖可抑制人淋巴管内皮细胞（HLECs）的增殖、迁移和管状结构形成，并在体外对肿瘤诱导的淋巴管生成具有抑制作用。此外，我们发现岩藻依聚糖对HLECs中PROX1、血管内皮生长因子受体3（VEGFR3）、核因子κB（NF-κB）、磷酸化磷脂酰肌醇-3激酶（phospho-PI3K）和磷酸化蛋白激酶B（phospho-Akt）的表达具有剂量依赖性抑制作用。此外，通过使用小鼠肿瘤模型评估了岩藻依聚糖的抗淋巴管生成作用。总之，岩藻依聚糖通过降低PROX1和VEGFR3的水平，抑制NF-κB/PI3K/Akt信号通路，从而抑制肿瘤淋巴管生成和淋巴转移。