Fucoxanthin Inhibits Migration And Invasion In U87 And U251 Cells Through Supression Of Beta-catenin-induced Cyclooxygenase-2/matrix Metallopeptidase-2/9 Singnaling

Backgroundand:Glioblastoma multiforme (GBM) are the most frequent primary tumors in human central nervous system .[1] Surgery combined with pharmacological inhibitors is the standard treatment for GBM [2;3]Despite the development of treatments, most malignant gliomas are resistant to pharmacological inhibitors and the median survival of patients with this tumor is 15 months[4] Thus, a novel therapeutic approach to cure this malignancy is in urgent need.p-catenin is the key molecule of the Wnt signaling pathway, which is well implicated in multiple tumors including GBM[5; 6;7] As previous report,β-catenin and its downstream signal ,such as COX2 ,MMP2/9 ,play a crucial role in migration and invasion of glioma that realated to the poor prognosis.[8;9;10]Thus it is urgent to develop chemotherapeutic agents targeting β-catenin to suppress the GMB.Fucoxanthin is a marine carotenoid that exhibiting various pharmacological activities including anti-cancer activity.[11;12;13]In the previous study, fucoxanthin can inhibit various cancers via multiple mechanism such as pro- apoptosis, cell cycle arrest,[14;15;16] however weather fucoxanthin can inhibit the glioma remains unknown. In present study, we demonstrated the antineoplastic activity of fucoxanthin on GMB in vitro. Furthermore,we focus on the effect on anti-invasion and anti-migration and investigated the underlying mechanisms.Objective: our study is aimed to explore it. In our study, fucoxanthin not only inhibited the proliferation, but also successfully repressed the migration and invasive ability in U87 and U251, two cell lines of GMB. Deeply, fucoxanthin decreased the β-catenin/Cyclooxygenase 2(COX2)/Matrix metallopeptidase 2/9(MMP2/9) signaling in 87 and U251. Furthermore, the U87 and U251 show partially resistance when overexpressed the β-catenin.Methods:MTT assayCell migration and invasion assaysGelatin zymography assayWestern blottingStatistical analysisResults:Fucoxanthin inhibits the viability of U87 and U251 cellsWe tested the effect of fucoxanthin on cell viability in U87 and U251 cells using the MTT assay. Incubation of both cell lines with fucoxanthin at concentrations ranging from 25 μ to 100μM for 12, 24 hours significantly decreased cell viability. In comparison to the control cells, the values of cell viability were 86.82%, 71.12%, 37.36%when U87 cells were treated with fucoxanthin at 25, 50, and 100 μM for 24 hours,respectively (Figure 1A). In parallel, the values of cell viability of U251 cells were 71.68%, 55.76%, 38.1%, 20.62% respectively (Figure 1B). The results indicate that fucoxanthin has a powerful inhibitory effect on cell proliferation in U87 and U251 cells.Fucoxanthin inhibits migration and invasion of U87 and U251 cells Fcoxanthin suppress the β-catenin/cox2/MMP2/9 pathway ectopic expression of β-catenin in U87 and U251 cells abolish the anticancer activity of fcoxanthinconclusion : we report fucoxanthin can effectively inhibit GMB via anti-proliferation, anti-migration and anti-invasion in vitro. Furthermore, we demonstrate the fucoxanthin-induced inhibition of MMP2/9 and COX2 is regulated,at least in part,by β-catenin. We thus conclude fucoxanthin is a hopeful chemical agent to cure glioma.