title: Sargassum fusiforme polysaccharides inhibit VEGF-A-related angiogenesis and proliferation of lung cancer in vitro and in vivo.
abstract: Sargassum fusiforme (Harv.) is a brown alga belonging to the Sargasaceae family. The Sargassum fusiforme polysaccharides (SFPS) have demonstrated good anti-tumor and immunomodulatory activity. However, the underlying mechanisms of its anti-tumorigenesis, especially the anti-angiogenic activity is yet to be established. In the present study, we attempted to determine the effects of SFPS on the human lung adenocarcinoma SPC-A-1 cells and its xenograft model. The results showed that SFPS provides a concentration-dependent inhibition of SPC-A-1 cell proliferation in in vitro and the tumor growth in in vivo studies. Immunohistochemistry studies revealed that the administration of SFPS significantly decreased CD31, VEGF-A expression and the tumor microvessel density (MVD). SFPS also provided a dose-dependent impairment of cell vitality, induction of cell cycle arrest and apoptosis of human umbilical vein endothelial cells (HUVECs). SFPS inhibited the expression of VEGF-A in tumor cells and its receptor VEGFR2 in HUVECs. The HUVEC tube formation assay showed that SFPS could abrogate the tube formation with relatively decreased tubes length of tube-like capillary similar to anti-VEGF antibody, Avastin®. These findings suggested that SFPS could be used as an alternative anticancer drug as they inhibited the angiogenesis and the microvessel formation through disruption of VEGF signals apart from direct tumor cytotoxicity.
authors.affiliation: Department of Physiology, College of Medical, Ningbo College of Health Sciences, Ningbo 315010, China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Physiology, College of Medical, Ningbo College of Health Sciences, Ningbo 315010, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Physiology, College of Medical, Ningbo College of Health Sciences, Ningbo 315010, China.
authors.forename: Xiange
authors.initials: X
authors.lastname: Long
authors.affiliation: Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China.
authors.forename: Peifei
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China.
authors.forename: Shengcan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Physiology, College of Medical, Ningbo College of Health Sciences, Ningbo 315010, China. Electronic address: kwei93@hotmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Kuang
authors.affiliation: Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China.
authors.forename: Junming
authors.initials: J
authors.lastname: Guo
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000517:prevention & control*; D011134:Polysaccharides / Q000737:chemistry* / Q000627:therapeutic use; D011897:Random Allocation; D044647:Sargassum / Q000737:chemistry*; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D011134:Polysaccharides; D042461:Vascular Endothelial Growth Factor A
keywords: Apoptosis; Lung cancer; Sargassum fusiforme polysaccharides; Tumor microvessel density; VEGF