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The HDAC Inhibitor Vorinostat Diminishes the In Vitro Metastatic Behavior of Osteosarcoma Cells

Osteosarcoma (OS) is the most common primary malignancy of bone and affects patients in the first two decades of life. The greatest determinant of survival is the presence of pulmonary metastatic disease. The role of epigenetic regulation in OS, specifically the biology of metastases, is unknown. Ou...

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Detalles Bibliográficos
Autores principales: Mu, Xiaodong, Brynien, Daniel, Weiss, Kurt R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346695/
https://www.ncbi.nlm.nih.gov/pubmed/25785263
http://dx.doi.org/10.1155/2015/290368
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author Mu, Xiaodong
Brynien, Daniel
Weiss, Kurt R.
author_facet Mu, Xiaodong
Brynien, Daniel
Weiss, Kurt R.
author_sort Mu, Xiaodong
collection PubMed
description Osteosarcoma (OS) is the most common primary malignancy of bone and affects patients in the first two decades of life. The greatest determinant of survival is the presence of pulmonary metastatic disease. The role of epigenetic regulation in OS, specifically the biology of metastases, is unknown. Our previous study with the murine OS cell populations K7M2 and K12 demonstrated a significant correlation of metastatic potential with the DNA methylation level of tumor suppressor genes. In the current study, we investigated if the histone deacetylase (HDAC) inhibitor, vorinostat, could regulate the metastatic potential of highly metastatic OS cells. Our results revealed that vorinostat treatment of highly metastatic K7M2 OS cells was able to greatly reduce the proliferation and metastatic potential of the cells. Morphological features related to cell motility and invasion were changed by vorinostat treatment. In addition, the gene expressions of mTOR, ALDH1, and PGC-1 were downregulated by vorinostat treatment. These data suggest that vorinostat may be an effective modulator of OS cell metastatic potential and should be studied in preclinical models of metastatic OS.
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spelling pubmed-43466952015-03-17 The HDAC Inhibitor Vorinostat Diminishes the In Vitro Metastatic Behavior of Osteosarcoma Cells Mu, Xiaodong Brynien, Daniel Weiss, Kurt R. Biomed Res Int Research Article Osteosarcoma (OS) is the most common primary malignancy of bone and affects patients in the first two decades of life. The greatest determinant of survival is the presence of pulmonary metastatic disease. The role of epigenetic regulation in OS, specifically the biology of metastases, is unknown. Our previous study with the murine OS cell populations K7M2 and K12 demonstrated a significant correlation of metastatic potential with the DNA methylation level of tumor suppressor genes. In the current study, we investigated if the histone deacetylase (HDAC) inhibitor, vorinostat, could regulate the metastatic potential of highly metastatic OS cells. Our results revealed that vorinostat treatment of highly metastatic K7M2 OS cells was able to greatly reduce the proliferation and metastatic potential of the cells. Morphological features related to cell motility and invasion were changed by vorinostat treatment. In addition, the gene expressions of mTOR, ALDH1, and PGC-1 were downregulated by vorinostat treatment. These data suggest that vorinostat may be an effective modulator of OS cell metastatic potential and should be studied in preclinical models of metastatic OS. Hindawi Publishing Corporation 2015 2015-02-17 /pmc/articles/PMC4346695/ /pubmed/25785263 http://dx.doi.org/10.1155/2015/290368 Text en Copyright © 2015 Xiaodong Mu et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Mu, Xiaodong
Brynien, Daniel
Weiss, Kurt R.
The HDAC Inhibitor Vorinostat Diminishes the In Vitro Metastatic Behavior of Osteosarcoma Cells
title The HDAC Inhibitor Vorinostat Diminishes the In Vitro Metastatic Behavior of Osteosarcoma Cells
title_full The HDAC Inhibitor Vorinostat Diminishes the In Vitro Metastatic Behavior of Osteosarcoma Cells
title_fullStr The HDAC Inhibitor Vorinostat Diminishes the In Vitro Metastatic Behavior of Osteosarcoma Cells
title_full_unstemmed The HDAC Inhibitor Vorinostat Diminishes the In Vitro Metastatic Behavior of Osteosarcoma Cells
title_short The HDAC Inhibitor Vorinostat Diminishes the In Vitro Metastatic Behavior of Osteosarcoma Cells
title_sort hdac inhibitor vorinostat diminishes the in vitro metastatic behavior of osteosarcoma cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346695/
https://www.ncbi.nlm.nih.gov/pubmed/25785263
http://dx.doi.org/10.1155/2015/290368
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