Abstract
BackgroundFucoidan, a water-soluble polysaccharide, exerts anticoagulant and antiviral functions. It was recently reported that fucoidan also exerts an antitumor function. Lung cancer is one of the most common cancers in the world. The aim of this study was to investigate anti-tumor,apoptosis and anti-metastasis effects of fucoidan in both cell-based assays and mouse xenograft model, as well as to clarify possible role of m-TOR pathway in the protection.MethodsIn vitro: Different concentrations of fucoidan were given to act on non-small cell lung cancer (NSCLC) cell lines A549 and H1650. The effects of fucoidan on cell proliferation were observed by detecting cyclin expression levels, CCK8 and EDU experiments and cloning experiments. The apoptotic level was detected by flow cytometry and the apoptotic protein level was detected by Westernblot. By detecting the expression of adhesion molecules, the expression of matrix metalloproteinase (MMP) family, and Transwell cell invasion and migration experiment, the effect of fucoidan on cell adhesion, invasion and migration was observed. Meanwhile the effect of fucoidan on angiogenesis was observed by detecting the expression of vascular endothelial growth factor (VEGF).In vivo experiment: An animal model of NSCLC cell mouse subcutaneous xenograft tumor was established to analyze the correlation between the consumption of fucoidan and the size and volume of xenograft tumor through gross observation. Through immunohistochemical staining and immunofluorescence double staining, ki67 and cell adhesion molecules (E-cadherin, N-cadherin and CD31) and VEGF-A in the tumor were detected, and the correlation between the amount of fucoidan and the above indexes was analyzed.ResultsFucoidan inhibited the proliferation and angiogenesis of NSCLC cells via the mTOR pathway and promoted their apoptosis by increasing the Bax/Bcl-2 ratio. Not only that, fucoidan inhibited NSCLC cell invasion via epithelial–mesenchymal transformation (EMT). The mice fed fucoidan exhibited significant reductions in tumor volumes and weights. These indicators (Ki67, VEGF-A,N-cadherin) were decreased and E-cadherin expression was up-regulated in A549 mice that treated with fucoidan. The results showed that fucoidan inhibited tumor proliferation in vivo by affecting the expression of related proteins.ConclusionFucoidan conveys antitumor effects and our results represent an ideal therapeutic agent for NSCLC.
Highlights
Fucoidan, a water-soluble polysaccharide, exerts anticoagulant and antiviral functions
Fucoidan inhibits cell proliferation and vascular endothelial growth factor (VEGF) expression in A549 and H1650 cells To clarify whether fucoidan influences the proliferation ability of Nonsmall cell lung cancer (NSCLC) cells, we treated A549 and H1650 cells with 10 and 16 mg/ml fucoidan for 4 days
The OD values of the CCK8 assay showed a significant decrease in the proliferation of A549 and H1650 cells compared with control cells (Fig. 1a)
Summary
A water-soluble polysaccharide, exerts anticoagulant and antiviral functions. The aim of this study was to investigate anti-tumor,apoptosis and anti-metastasis effects of fucoidan in both cell-based assays and mouse xenograft model, as well as to clarify possible role of m-TOR pathway in the protection. Fucoidan has been shown to alleviate metabolic syndrome [8], benefit angiogenesis [9] and bone health [10].Besides,a number of studies have confirmed that fucoidan exerts antitumor effects. In previous in vivo studies conducted using xenograft models, study demonstrated that fucoidan can significantly hinder the tumor growth and inhibited angiogenesis of prostate cancer cells DU145 [14]. The antitumor effect of fucoidan in non-small cell lung cancer has not been elucidated and the mechanism is controversial because it is uncertain which cascade plays a pivotal role in the induction of tumor growth by fucoidan. We built an NSCLC A549 cell xenograft mouse model to observe the influence of fucoidan on NSCLC tumor growth and further verified the function of fucoidan in animal models
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