Effects of homoharringtonine on the migration and invasion ability of human triple negative breast cancer cells
Objective To investigate the effects of homoharringtonine(HHT)on migration and invasion of human triple nega-tive breast cancer(TNBC)cell line MDA-MB-231,and to analyze the potential mechanisms.Methods MTT assay was used to de-tect cell viability.EdU incorporation assay was used to evaluate cell proliferation.Cell scratch assay and Transwell assay were used to detect cell migration and invasion respectively.Flow cytometry was used to analyze the content of breast cancer stem cells(BCSC).Sphere formation test was used to evaluate the ability of MDA-MB-231 cells to form tumor spheres.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect Gli1 mRNA and the mRNA expression of Oct4,CD44,Sox2 and Nanog in breast cancer cells.Western blotting was used to analyze the expression of EMT markers E-cadherin,N-cadherin,Vimentin and Gil1 protein.Results Homoharringtonine decreased the viability of MDA-MB-231 cells in a dose-dependent manner(P＜0.05).Homoharringtonine could in-hibit the proliferation,migration and invasion of BC cells.In addition,homoharringtonine could down-regulate the ratio of CD44+/CD24-cells in BC cells,decreased the ability of MDA-MB-231 cells to form tumor balls,and inhibited the mRNA expressions of Oct4,CD44,Sox2 and Nanog,suggesting that homoharringtonine could inhibit the dryness of MDA-MB-231 cells.Homoharringtonine could inhibit EMT of BCSC by inhibiting E-cadherin expression and increasing N-cad-herin and Vimentin proteins in tumor spheres.In addition,homoharringtonine could inhibit the activation of HH/Gli1 signaling pathway in TNBC.Meanwhile,homoharringtonine could eliminate the effects of Gli1 overexpression on TNBC stemness and EMT.Conclu-sion Homoharringtonine can inhibit the migration and invasion of breast cancer cells,which may be achieved by regulating HH/Gli1 signaling pathway to inhibit TNBC stemness and EMT.
homoharringtoninetriple negative breast cancermigration and invasionHH/Gli1 signaling pathwaybreast can-cer stem cellsepithelial mesenchymal transition
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