title: A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1-MMP via the Wnt signaling pathway.
abstract: This study aimed to explore the exact mechanism of the effect of a furin inhibitor on the migration and invasion of MG-63 and Saos-2 osteosarcoma cells. MG-63 and Saos-2 osteosarcoma cells were treated with regular culture medium in the presence or absence of 480 nM α1-antitrypsin Portland (α1-PDX). Wound-healing and Transwell assays were used for the detection of the effects of α1-PDX on MG-63 and Saos-2 osteosarcoma cell migration and invasion. Western blot analysis and reverse transcription-polymerase chain reaction were performed to detect the expression levels of membrane type I matrix metalloproteinase (MT1-MMP), Wnt and β-catenin. A chromatin immunoprecipitation assay was used for detection of the levels of MT1-MMP gene transcription activity. The results showed that α1-PDX treatment significantly reduced the migration and invasion ability of the cells. Notably, the expression levels of MT1-MMP decreased evidently upon α1-PDX treatment, paralleled with reductions in the expression levels of Wnt and β-catenin. Further analysis of the transcriptional activity of MT1-MMP revealed that the α1-PDX-induced downregulation of the levels of MT1-MMP was mediated by the Wnt signaling pathway. These data suggest that α1-PDX plays a vital role in inhibiting MG-63 and Saos-2 osteosarcoma cell migration and invasion by downregulating the expression levels of MT1-MMP via the Wnt signaling pathway.
authors.affiliation: Department of Orthopaedics, Huaihe Hospital, Henan University, Kaifeng, Henan 475001, P.R. China.
authors.forename: Bingshan
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Huaihe Hospital, Henan University, Kaifeng, Henan 475001, P.R. China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Huaihe Hospital, Henan University, Kaifeng, Henan 475001, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Huaihe Hospital, Henan University, Kaifeng, Henan 475001, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
keywords: MT1-MMP; Wnt; migration; osteosarcoma MG-63 and Saos-2; α1-PDX; β-catenin