Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells
Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells
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DOI：
10.1016/j.phymed.2017.09.014
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发表时间：
2017-12-01
期刊：
影响因子：
7.9
通讯作者：
Wongprasert, Kanokpan
中科院分区：
文献类型：
--
作者：
Sae-lao, Thannicha;Luplertlop, Natthanej;Wongprasert, Kanokpan
背景：海藻在亚洲国家作为功能性食品、草药和治疗癌症有着悠久的历史。海藻多糖具有抗肿瘤活性。胆管癌（CCA），往往与转移性疾病，是高度流行的结果，在泰国的肝吸虫感染。最近，我们从江蓠（Gracilariaacutani，G.目的：探讨SG对CCA细胞迁移的抑制作用及其作用机制。方法：将CCA细胞分别用SG单独处理、表皮生长因子（EGF）受体（EGFR）靶向药物处理或SG预处理后与EGF共同孵育。使用划痕伤口愈合测定和酶谱法测定抗迁移活性。免疫荧光染色和蛋白质印迹法被用来调查EGFR信号mediators.Results：在基础条件下，SG降低CCA的迁移率，这是与基质金属蛋白酶-9的活性形式的减少。SG降低磷酸化粘着斑激酶（FAK）的表达，但增加E-钙粘蛋白的表达，促进细胞停滞。此外，已知刺激癌细胞生长的EGFR和细胞外信号调节激酶（ERK）的磷酸化以与EGFR抑制剂西妥昔单抗和厄洛替尼相当的方式被阻断。SG预处理细胞可减弱EGF诱导的EGFR、ERK和FAK的磷酸化。结果表明，人参皂甙对CCA细胞的迁移有抑制作用，其机制可能与抑制MAPK/ERK信号转导通路有关。我们的研究结果表明，可能有一个治疗潜力的SG在CCA治疗。
Background: Seaweeds have a long history of use in Asian countries as functional foods, medicinal herbs, and the treatment of cancer. Polysaccharides from various seaweeds have shown anti-tumor activity. Cholangiocarcinoma (CCA), often with metastatic disease, is highly prevalent in Thailand as a consequence of liver fluke infection. Recently, we extracted sulfated galactans (SG) from Gracilaria fisheri (G. fisheri), a south east Asian seaweed, and found it exhibited anti-proliferation effect on CCA cells.Purpose: In the present study, we evaluated the anti-migration activity of SG on CCA cells and its underlined mechanism.Methods: CCA cells were treated with SG alone or drugs targeting to epidermal growth factor (EGF) receptor (EGFR) or pretreated with SG prior to incubation with EGF. Anti-migration activity was determined using a scratch wound-healing assay and zymography. Immunofluorescence staining and western blotting were used to investigate EGFR signaling mediators.Results: Under basal condition, SG reduced the migration rate of CCA, which was correlated with a decrease in the active-form of matrix metalloproteinases-9. SG decreased expression of phosphorylated focal adhesion kinase (FAK), but increased expression of E-cadherin to promote cells stasis. Moreover, phosphorylation of EGFR and extracellular signal-regulated kinases (ERK), known to stimulate growth of cancer cells, was blocked in a comparable way to EGFR inhibitors Cetuximab and Erlotinib. Pretreatment cells with SG attenuated EGF induced phosphorylation of EGFR, ERK and FAK.Conclusion: This study reveals that SG from G. fisheri retards migration of CCA cells, and its mechanism of inhibition is mediated, to some extent, by inhibitory effects on MAPK/ERK signal transduction pathway. Our findings suggest that there may be a therapeutic potential of SG in CCA treatment.