The sulfated polysaccharide fucoidan displays excellent anticancer properties with low toxicity in many kinds of cancers. However, its detailed pharmacological effect and mechanism of action in gastric carcinoma remains unclear. In this study, we found that fucoidan could suppress gastric cancer (GC) cell growth, as well as cell migration and invasion. A cytokine expression screen demonstrated that transforming growth factor beta 1 (TGF-β1) secretion was decreased in fucoidan-treated cells. Fucoidan has been reported to be a platelet agonist for the C-type lectin-like receptor 2 (CLEC-2), and our previous research found that upregulation of CLEC-2 inhibited GC progression. Here, we confirmed that fucoidan, combined with CLEC-2, significantly increased CLEC-2 expression in GC cells via the transcription factor caudal type homeobox transcription factor 2, an important regulator of gut homeostasis. In addition, the inhibitory effect of fucoidan on the GC cell malignant phenotype and TGF-β1 secretion could be restored by knocking down CLEC-2. Thus, our data suggest that fucoidan targets CLEC-2 to exert antitumorigenesis and antimetastatic activity, suggesting that fucoidan is a promising treatment for gastric carcinoma.

中文翻译：

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Fucoidan通过CLEC-2抑制胃癌细胞的恶性表型和TGF-β1的产生。

硫酸多糖岩藻依聚糖在多种癌症中均显示出优异的抗癌特性，且毒性低。然而，其在胃癌中的详细药理作用和作用机理仍不清楚。在这项研究中，我们发现岩藻依聚糖可以抑制胃癌（GC）细胞的生长以及细胞的迁移和侵袭。细胞因子表达筛选表明，在岩藻依聚糖处理的细胞中，转化生长因子β1（TGF-β1）的分泌减少了。据报道，岩藻依丹是C型凝集素样受体2（CLEC-2）的血小板激动剂，而我们先前的研究发现，CLEC-2的上调抑制了GC的进程。在这里，我们确认岩藻依聚糖与CLEC-2结合使用，通过尾肠同源异型盒转录因子2（肠道稳态的重要调节剂），可显着增加GC细胞中CLEC-2的表达。此外，岩藻依聚糖对GC细胞恶性表型和TGF-β1分泌的抑制作用可通过敲低CLEC-2来恢复。因此，我们的数据表明岩藻依聚糖靶向CLEC-2发挥抗肿瘤作用和抗转移活性，表明岩藻依聚糖是胃癌的一种有前途的治疗方法。