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Inhibition of oleandrin on the proliferation show and invasion of osteosarcoma cells in vitro by suppressing Wnt/β-catenin signaling pathway

BACKGROUND: Osteosarcoma (OS) is a high-grade bone sarcoma with early metastasis potential, and the clinical chemotherapy drugs that are currently used for its treatment have some limitations. Recently, several studies have reported the selective antitumor effect of oleandrin on various tumor cells....

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Autores principales: Ma, Yunlong, Zhu, Bin, Liu, Xiaoguang, Yu, Huilei, Yong, Lei, Liu, Xiao, Shao, Jia, Liu, Zhongjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596494/
https://www.ncbi.nlm.nih.gov/pubmed/26444270
http://dx.doi.org/10.1186/s13046-015-0232-8
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author Ma, Yunlong
Zhu, Bin
Liu, Xiaoguang
Yu, Huilei
Yong, Lei
Liu, Xiao
Shao, Jia
Liu, Zhongjun
author_facet Ma, Yunlong
Zhu, Bin
Liu, Xiaoguang
Yu, Huilei
Yong, Lei
Liu, Xiao
Shao, Jia
Liu, Zhongjun
author_sort Ma, Yunlong
collection PubMed
description BACKGROUND: Osteosarcoma (OS) is a high-grade bone sarcoma with early metastasis potential, and the clinical chemotherapy drugs that are currently used for its treatment have some limitations. Recently, several studies have reported the selective antitumor effect of oleandrin on various tumor cells. In this study, we aimed to evaluate the effects and underlying mechanisms of oleandrin on OS cells. METHODS: The effect of oleandrin on the proliferation, morphology, and apoptosis of U2OS and SaOS-2 cells were analyzed in vitro. The activity of the Wnt/β-catenin signaling pathway was determined using a dual luciferase assay. Semi-quantitative RT-PCR and western blot assays were performed to evaluate the mRNA and total protein expression of the downstream target genes. Changes of β-catenin in intracellular localization were also explored using a western blot after separating the nucleus and cytoplasm proteins. The MMP-2 and MMP-9 enzymatic activities were determined using gelatin zymography. RESULTS: Oleandrin significantly inhibited the proliferation and invasion of OS cells in vitro, and induced their apoptosis. After treatment with oleandrin, the TOP/FOP flash ratio in OS cells was noticeably decreased, which indicated that the Wnt/β-catenin signaling pathway was repressed. The expression of related Wnt target genes and total β-catenin was downregulated, and a reduced nuclear β-catenin level by oleandrin was observed as well. In addition, oleandrin suppressed the activities of MMP-2 and MMP-9. CONCLUSIONS: Oleandrin, in vitro, exerted a strong antitumor effect on human OS cells by suppressing the Wnt/β-catenin signaling pathway, which interfered with the proliferation and invasion of OS cells, as well as induced cells apoptosis. Moreover, the expression and activities of MMP-2 and MMP-9 were downregulated by oleandrin, which contributed to the cells’ lower invasiveness.
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spelling pubmed-45964942015-10-08 Inhibition of oleandrin on the proliferation show and invasion of osteosarcoma cells in vitro by suppressing Wnt/β-catenin signaling pathway Ma, Yunlong Zhu, Bin Liu, Xiaoguang Yu, Huilei Yong, Lei Liu, Xiao Shao, Jia Liu, Zhongjun J Exp Clin Cancer Res Research BACKGROUND: Osteosarcoma (OS) is a high-grade bone sarcoma with early metastasis potential, and the clinical chemotherapy drugs that are currently used for its treatment have some limitations. Recently, several studies have reported the selective antitumor effect of oleandrin on various tumor cells. In this study, we aimed to evaluate the effects and underlying mechanisms of oleandrin on OS cells. METHODS: The effect of oleandrin on the proliferation, morphology, and apoptosis of U2OS and SaOS-2 cells were analyzed in vitro. The activity of the Wnt/β-catenin signaling pathway was determined using a dual luciferase assay. Semi-quantitative RT-PCR and western blot assays were performed to evaluate the mRNA and total protein expression of the downstream target genes. Changes of β-catenin in intracellular localization were also explored using a western blot after separating the nucleus and cytoplasm proteins. The MMP-2 and MMP-9 enzymatic activities were determined using gelatin zymography. RESULTS: Oleandrin significantly inhibited the proliferation and invasion of OS cells in vitro, and induced their apoptosis. After treatment with oleandrin, the TOP/FOP flash ratio in OS cells was noticeably decreased, which indicated that the Wnt/β-catenin signaling pathway was repressed. The expression of related Wnt target genes and total β-catenin was downregulated, and a reduced nuclear β-catenin level by oleandrin was observed as well. In addition, oleandrin suppressed the activities of MMP-2 and MMP-9. CONCLUSIONS: Oleandrin, in vitro, exerted a strong antitumor effect on human OS cells by suppressing the Wnt/β-catenin signaling pathway, which interfered with the proliferation and invasion of OS cells, as well as induced cells apoptosis. Moreover, the expression and activities of MMP-2 and MMP-9 were downregulated by oleandrin, which contributed to the cells’ lower invasiveness. BioMed Central 2015-10-06 /pmc/articles/PMC4596494/ /pubmed/26444270 http://dx.doi.org/10.1186/s13046-015-0232-8 Text en © Ma et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Ma, Yunlong
Zhu, Bin
Liu, Xiaoguang
Yu, Huilei
Yong, Lei
Liu, Xiao
Shao, Jia
Liu, Zhongjun
Inhibition of oleandrin on the proliferation show and invasion of osteosarcoma cells in vitro by suppressing Wnt/β-catenin signaling pathway
title Inhibition of oleandrin on the proliferation show and invasion of osteosarcoma cells in vitro by suppressing Wnt/β-catenin signaling pathway
title_full Inhibition of oleandrin on the proliferation show and invasion of osteosarcoma cells in vitro by suppressing Wnt/β-catenin signaling pathway
title_fullStr Inhibition of oleandrin on the proliferation show and invasion of osteosarcoma cells in vitro by suppressing Wnt/β-catenin signaling pathway
title_full_unstemmed Inhibition of oleandrin on the proliferation show and invasion of osteosarcoma cells in vitro by suppressing Wnt/β-catenin signaling pathway
title_short Inhibition of oleandrin on the proliferation show and invasion of osteosarcoma cells in vitro by suppressing Wnt/β-catenin signaling pathway
title_sort inhibition of oleandrin on the proliferation show and invasion of osteosarcoma cells in vitro by suppressing wnt/β-catenin signaling pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596494/
https://www.ncbi.nlm.nih.gov/pubmed/26444270
http://dx.doi.org/10.1186/s13046-015-0232-8
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