A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1‑MMP via the Wnt signaling pathway

Liu,Bingshan; Li,Guojun; Wang,Xiao; Liu,Yang

doi:10.3892/ol.2014.1839

A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1‑MMP via the Wnt signaling pathway

Authors:
- Bingshan Liu
- Guojun Li
- Xiao Wang
- Yang Liu
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Affiliations: Department of Orthopaedics, Huaihe Hospital, Henan University, Kaifeng, Henan 475001, P.R. China
Published online on: January 29, 2014 https://doi.org/10.3892/ol.2014.1839
Pages: 1033-1038

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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.

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