Anti-metastatic effects of the sulfated polysaccharide ascophyllan isolated from Ascophyllum nodosum on B16 melanoma
Anti-metastatic effects of the sulfated polysaccharide ascophyllan isolated from Ascophyllum nodosum on B16 melanoma
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DOI：
10.1016/j.bbrc.2015.01.061
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发表时间：
2015-03-20
影响因子：
3.1
通讯作者：
Oda, Tatsuya
中科院分区：
文献类型：
--
作者：
Abu, Ryogo;Jiang, Zedong;Oda, Tatsuya
我们之前发现泡叶聚糖（一种从棕色海藻泡叶藻中分离出来的硫酸化多糖）在 sarcoma-180 荷瘤小鼠中表现出抗肿瘤活性。在本研究中，我们发现泡叶素通过降低N-钙粘蛋白的表达并增强E-钙粘蛋白的表达以浓度依赖性方式抑制B16黑色素瘤细胞的迁移和粘附。 Transwell侵袭实验显示泡叶素抑制B16细胞的侵袭能力。它还抑制 B16 细胞中基质金属蛋白酶 9 (MMP-9) mRNA 的表达和 MMP-9 蛋白的分泌，这一过程可能涉及细胞外信号调节激酶 (ERK) 信号通路。此外，腹腔注射25 mg/kg的泡叶素在静脉注射B16细胞诱导的转移小鼠模型中显示出抗转移活性，与未治疗的对照小鼠相比，泡叶素治疗的小鼠肺表面转移结节的数量显着减少。由于腹腔注射泡叶兰的小鼠脾脏自然杀伤细胞活性增强，我们认为泡叶兰除了直接作用于癌细胞外，还可能通过激活宿主免疫系统对 B16 黑色素瘤细胞表现出体内抗转移活性。 (C) 2015 Elsevier Inc. 保留所有权利。
We previously found that ascophyllan, a sulfated polysaccharide isolated from brown seaweed Ascophyllum nodosum, exhibited antitumor activity in sarcoma-180 tumor-bearing mice. In this study, we found that ascophyllan inhibited the migration and adhesion of B16 melanoma cells by reducing the expression of N-cadherin and enhancing the expression of E-cadherin in a concentration-dependent manner. Transwell invasion assay revealed that ascophyllan suppressed the invasion ability of B16 cells. It also inhibited the expression of matrix metalloprotease-9 (MMP-9) mRNA and the secretion of MMP-9 protein in B16 cells, a process that may involve the extracellular signal-regulated kinase (ERK) signaling pathway. Furthermore, ascophyllan administered intraperitoneally at 25 mg/kg showed anti-metastatic activity in a mouse model of metastasis induced by intravenous injection of B16 cells, and the number of lung surface metastatic nodules in ascophyllan-treated mice was significantly reduced compared to that in the untreated control mice. Since splenic natural killer cell activity enhanced in the mice injected with ascophyllan intraperitoneally, we suggest that ascophyllan may exhibit in vivo anti-metastatic activity on B16 melanoma cells through activation of the host immune system in addition to a direct action on cancer cells. (C) 2015 Elsevier Inc. All rights reserved.