期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 154, 期 -, 页码 72-81出版社
ELSEVIER
DOI: 10.1016/j.ijbiomac.2020.03.068
关键词
Sulfated polysaccharide; Anti-tumor angiogenic activity; VEGF/VEGFR signaling pathway
资金
- National Natural Science Foundation of China [81973218, 81402833]
- Natural Science Foundation of Shandong Province [ZR2019MH082]
- Key Research and Development Program of Shandong Province [2017GSF218100, 2015GSF119005]
Previous studies have demonstrated that the sulfated polysaccharide named PRP-S16 could inhibit the proliferation, migration, and tube formation of endothelial cells in vitro. Here, its anti-angiogenic effect and mechanism in vivo were investigated by Lewis lung carcinoma (LLC) mice model. PRP-S16 significantly reduced the microvessel density (MVD) of tumor, exhibiting a high tumor growth inhibitory effect in LLC mice. All designed assays including quantitative real-time PCR, immunohistochemistry, enzyme-linked immunosorbent assay and western blotting showed that PRP-S16 reduced the mRNA and the protein expression of vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) in serum or tumor tissue of mice. Western blotting also detected decreased phosphorylated (p)-VEGFR-1, p-VEGFR-2, hypoxia-inducible factor-1 alpha (HIF-1 alpha), protein kinase B (Akt), and matrix metalloproteinases-9 (MMP-9). PRP-S16 had no adverse effects on angiogenesis in nontarget organs. These findings suggested that the mechanism of anti-angiogenesis of PRP-S16 in vivo was due to inhibition of VEGF/VEGFR signaling pathway and it might be a promising candidate for tumor by antiangiogenic therapy. (C) 2020 Published by Elsevier B.V.
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