Anticancer Properties and Mechanisms of Fucoidan on Mouse Breast Cancer In Vitro and In Vivo

被引:125
作者
Xue, Meilan [1 ]
Ge, Yinlin [1 ]
Zhang, Jinyu [1 ]
Wang, Qing [2 ]
Hou, Lin [1 ]
Liu, Yongchao [1 ]
Sun, Lingling [3 ]
Li, Quan [1 ]
机构
[1] Qingdao Univ, Coll Med, Dept Biochem & Mol Biol, Qingdao 266071, Peoples R China
[2] Qingdao Univ, Affiliated Hosp, Dept Ophthalmol, Qingdao 266071, Peoples R China
[3] Qingdao Univ, Affiliated Hosp, Dept Pathol, Qingdao 266071, Peoples R China
关键词
CLADOSIPHON-OKAMURANUS-TOKIDA; BROWN SEAWEED; SARGASSUM-THUNBERGII; ANTITUMOR-ACTIVITY; CELL-DEATH; APOPTOSIS; POLYSACCHARIDE; METASTASIS; INHIBITION; ACTIVATION;
D O I
10.1371/journal.pone.0043483
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: Fucoidan is a sulfated polysaccharide derived from brown algae that has been reported to perform multiple biological activities, including antitumor activity. In this study, we examined the influence of crude fucoidan on mouse breast cancer in vitro and in vivo. Materials and Methods: In vitro, fluorescent staining, flow cytometry and Western blot were performed to analyze apoptosis and vascular endothelial growth factor (VEGF) expression of mouse breast cancer 4T1 cells. In vivo, therapy experiments were conducted on Babl/c mice bearing breast cancer. The tumor volume and weight were measured. The number of apoptotic cells and microvascular density (MVD) in tumor tissues were assessed by TUNEL and CD34 immunostaining. Immunohistochemical assays and ELISA assay were used to detect the expression of VEGF in tissues. Results: In vitro studies showed that crude fucoidan significantly decreased the viable number of 4T1 cells, induced apoptosis and down-regulated the expression of VEGF. The expression of Bcl-2 was decreased, and the ratio of Bcl-2 to Bax was significantly decreased. The expression of Survivin and phosphorylated extracellular signal regulated protein kinases (ERKs) was decreased. Cytochrome C was released from mitochondria into cytosol, and the cleaved Caspase-3 protein rose after fucoidan treatment. Intraperitoneal injection of fucoidan in breast cancer models reduced the tumor volume and weight. The enhanced antitumor efficacy was associated with decreased angiogenesis and increased induction of apoptosis. Conclusion: These findings indicated that crude fucoidan inhibited mouse breast cancer growth in vitro and in vivo. These data suggest that fucoidan may serve as a potential therapeutic agent for breast cancer.
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页数:9
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