首页|TRAIL and Celastrol Combinational Treatment Suppresses Proliferation,Migration,and Invasion of Human Glioblastoma Cells via Targeting Wnt/β-Catenin Signaling Pathway
TRAIL and Celastrol Combinational Treatment Suppresses Proliferation,Migration,and Invasion of Human Glioblastoma Cells via Targeting Wnt/β-Catenin Signaling Pathway
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Objective:To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma cells.Methods:Cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16 μmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5 μmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5 μmol/L).Cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,respectively.Quantitative reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona oocludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 moVL)and the mechanism for action of TCCT was explored.Results:Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(P＜0.01).TCCT up-regulated the expression of GSK-3 β and down-regulated the expression of β-catenin and its associated proteins(P＜0.05 or P＜0.01),including c-Myc,Cyclin-D1,and matrix metalloproteinase(MMP)-2.In addition,LiCl,an activator of the Wnt signaling pathway,restored the inhibitory effects of TCCT on the expression of β-catenin and its downstream genes,as well as the migration and invasion of glioblastoma cells(P＜0.05 or P＜0.01).Conclusions:Celastrol and TRAIL can synergistically suppress glioblastoma cell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin pathway.This underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.
Research Center of Neuroscience,School of Basic Medical Sciences,Chongqing Medical University,Chongqing(400016),China
Laboratory of Developmental Biology,Department of Cell Biology and Genetics,School of Basic Medical Sciences,Chongqing Medical University,Chongqing(400016),China
Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Chongqing Medical University,Chongqing(400016),China
Scientific and Technological Research Programme of Chongqing Municipal Education Commission,China
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