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在携带Lewis肿瘤的小鼠中,岩藻依聚糖的预防性给药通过抑制血管内皮生长因子(VEGF)和基质金属蛋白酶(MMPs)来抑制癌症转移。

Prophylactic administration of fucoidan represses cancer metastasis by inhibiting vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in Lewis tumor-bearing mice.

作者信息

Huang Tse-Hung, Chiu Yi-Han, Chan Yi-Lin, Chiu Ya-Huang, Wang Hang, Huang Kuo-Chin, Li Tsung-Lin, Hsu Kuang-Hung, Wu Chang-Jer

机构信息

Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung 20401, Taiwan.

Graduate Institute of Clinical Medicine Sciences, Chang Gung University, Taoyuan 33302, Taiwan.

出版信息

Mar Drugs. 2015 Apr 3;13(4):1882-900. doi: 10.3390/md13041882.

Abstract

Fucoidan, a heparin-like sulfated polysaccharide, is rich in brown algae. It has a wide assortment of protective activities against cancer, for example, induction of hepatocellular carcinoma senescence, induction of human breast and colon carcinoma apoptosis, and impediment of lung cancer cells migration and invasion. However, the anti-metastatic mechanism that fucoidan exploits remains elusive. In this report, we explored the effects of fucoidan on cachectic symptoms, tumor development, lung carcinoma cell spreading and proliferation, as well as expression of metastasis-associated proteins in the Lewis lung carcinoma (LLC) cells-inoculated mice model. We discovered that administration of fucoidan has prophylactic effects on mitigation of cachectic body weight loss and improvement of lung masses in tumor-inoculated mice. These desired effects are attributed to inhibition of LLC spreading and proliferation in lung tissues. Fucoidan also down-regulates expression of matrix metalloproteinases (MMPs), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and vascular endothelial growth factor (VEGF). Moreover, the tumor-bearing mice supplemented with fucoidan indeed benefit from an ensemble of the chemo-phylacticity. The fact is that fucoidan significantly decreases viability, migration, invasion, and MMPs activities of LLC cells. In summary, fucoidan is suitable to act as a chemo-preventative agent for minimizing cachectic symptoms as well as inhibiting lung carcinoma metastasis through down-regulating metastatic factors VEGF and MMPs.

摘要

岩藻依聚糖是一种类肝素硫酸化多糖,富含于褐藻中。它具有多种抗癌保护活性,例如,诱导肝癌细胞衰老、诱导人乳腺癌和结肠癌细胞凋亡,以及阻碍肺癌细胞的迁移和侵袭。然而,岩藻依聚糖发挥作用的抗转移机制仍不清楚。在本报告中,我们在接种Lewis肺癌(LLC)细胞的小鼠模型中,探究了岩藻依聚糖对恶病质症状、肿瘤发展、肺癌细胞扩散和增殖以及转移相关蛋白表达的影响。我们发现,给予岩藻依聚糖对减轻接种肿瘤小鼠的恶病质体重减轻和改善肺部肿块具有预防作用。这些预期效果归因于抑制LLC在肺组织中的扩散和增殖。岩藻依聚糖还下调基质金属蛋白酶(MMPs)、活化B细胞核因子κB(NF-κB)和血管内皮生长因子(VEGF)的表达。此外,补充岩藻依聚糖的荷瘤小鼠确实受益于一系列化学预防性作用。事实上,岩藻依聚糖显著降低LLC细胞的活力、迁移、侵袭和MMPs活性。总之,岩藻依聚糖适合作为一种化学预防剂,通过下调转移因子VEGF和MMPs来减轻恶病质症状并抑制肺癌转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/560a/4413192/b98f374e53a1/marinedrugs-13-01882-g001.jpg

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