关键词: Ascophyllan Ascophyllum nodosum B16 melanoma Melanoma metastasis Sulfated polysaccharide

Mesh : Adjuvants, Immunologic / chemistry therapeutic use Animals Anticarcinogenic Agents / chemistry therapeutic use Ascophyllum / chemistry Cell Line, Tumor Killer Cells, Natural / drug effects immunology Lung / drug effects immunology metabolism pathology Lung Neoplasms / immunology metabolism prevention & control secondary MAP Kinase Signaling System / drug effects Male Matrix Metalloproteinase 9 / metabolism Melanoma, Experimental / drug therapy immunology metabolism pathology Mice Mice, Inbred C57BL Neoplasm Invasiveness / immunology pathology prevention & control Polysaccharides / chemistry therapeutic use Spleen / cytology

来  源:   DOI:10.1016/j.bbrc.2015.01.061   PDF(Sci-hub)

Abstract:
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.
摘要:
我们之前发现过的,一种从褐藻夜蛾中分离出的硫酸化多糖,在肉瘤180荷瘤小鼠中表现出抗肿瘤活性。在这项研究中,我们发现,通过降低N-cadherin的表达和增强E-cadherin的表达,以浓度依赖的方式抑制B16黑色素瘤细胞的迁移和粘附。Transwell细胞侵袭实验显示,蛇床子抑制了B16细胞的侵袭能力。抑制B16细胞基质金属蛋白酶-9(MMP-9)mRNA的表达和MMP-9蛋白的分泌,可能涉及细胞外信号调节激酶(ERK)信号通路的过程。此外,在静脉注射B16细胞诱导的小鼠转移模型中,以25mg/kg腹膜内施用的天麻素显示出抗转移活性,与未治疗的对照小鼠相比,接受过冬冬草多糖治疗的小鼠的肺表面转移结节数量显着减少。由于腹膜内注射ascophyllan的小鼠的脾自然杀伤细胞活性增强,我们认为,除了直接作用于癌细胞外,通过激活宿主免疫系统,天花可能对B16黑色素瘤细胞具有体内抗转移活性。
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