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17-AAG synergizes with Belinostat to exhibit a negative effect on the proliferation and invasion of MDA-MB-231 breast cancer cells

Breast cancer is one of the most common malignancies that threaten the health of women. Although there are a few chemotherapies for the clinical treatment of breast cancer, these therapies are faced with the problems of drug-resistance and metastasis. Drug combination can help to reduce the adverse...

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Autores principales: Zuo, Yu, Xu, Heng, Chen, Zhifeng, Xiong, Fengmin, Zhang, Bei, Chen, Kaixian, Jiang, Hualiang, Luo, Cheng, Zhang, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160548/
https://www.ncbi.nlm.nih.gov/pubmed/32236631
http://dx.doi.org/10.3892/or.2020.7563
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author Zuo, Yu
Xu, Heng
Chen, Zhifeng
Xiong, Fengmin
Zhang, Bei
Chen, Kaixian
Jiang, Hualiang
Luo, Cheng
Zhang, Hao
author_facet Zuo, Yu
Xu, Heng
Chen, Zhifeng
Xiong, Fengmin
Zhang, Bei
Chen, Kaixian
Jiang, Hualiang
Luo, Cheng
Zhang, Hao
author_sort Zuo, Yu
collection PubMed
description Breast cancer is one of the most common malignancies that threaten the health of women. Although there are a few chemotherapies for the clinical treatment of breast cancer, these therapies are faced with the problems of drug-resistance and metastasis. Drug combination can help to reduce the adverse side effects of chemotherapies using single drugs, and also help to overcome common drug-resistance during clinical treatment of breast cancer. The present study reported the synergistic effect of the heat shock protein 90 inhibitor 17-AAG and the histone deacetylase 6 inhibitor Belinostat in triple-negative breast cancer (TNBC) MDA-MB-231 cells, by detection of proliferation, apoptosis and cell cycle arrest following treatment with this combination. Subsequently, RNA sequencing (RNA-seq) data was collected and analyzed to investigate the synergistic mechanism of this combination. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways revealed by RNA-seq data analysis, a wound-healing assay was used to investigate the effect of this combination on the migration of MDA-MB-231 cells. Compared with treatment with 17-AAG or Belinostat alone, both the viability inhibition and apoptosis rate of MDA-MB-231 cells were significantly enhanced in the combination group. The combination index values were <1 in three concentration groups. Revealed by the RNA-seq data analysis, the most significantly enriched KEGG pathways in the combination group were closely associated with cell migration. Based on these findings, the anti-migration effect of this combination was investigated. It was revealed that the migration of MDA-MB-231 cells was significantly suppressed in the combination group compared with in the groups treated with 17-AAG or Belinostat alone. In terms of specific genes, the mRNA expression levels of TEA domain family proteins were significantly decreased in the combination group, whereas the phosphorylation of YY1 associated protein 1 and modulator of VRAC current 1 was significantly enhanced in the combination group. These alterations may help to explain the anti-migration effect of this combination. Belinostat has already been approved as a treatment for T-cell lymphoma and 17-AAG is undergoing clinical trials. These findings could provide a beneficial reference for the clinical treatment of patients with TNBC.
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spelling pubmed-71605482020-04-17 17-AAG synergizes with Belinostat to exhibit a negative effect on the proliferation and invasion of MDA-MB-231 breast cancer cells Zuo, Yu Xu, Heng Chen, Zhifeng Xiong, Fengmin Zhang, Bei Chen, Kaixian Jiang, Hualiang Luo, Cheng Zhang, Hao Oncol Rep Articles Breast cancer is one of the most common malignancies that threaten the health of women. Although there are a few chemotherapies for the clinical treatment of breast cancer, these therapies are faced with the problems of drug-resistance and metastasis. Drug combination can help to reduce the adverse side effects of chemotherapies using single drugs, and also help to overcome common drug-resistance during clinical treatment of breast cancer. The present study reported the synergistic effect of the heat shock protein 90 inhibitor 17-AAG and the histone deacetylase 6 inhibitor Belinostat in triple-negative breast cancer (TNBC) MDA-MB-231 cells, by detection of proliferation, apoptosis and cell cycle arrest following treatment with this combination. Subsequently, RNA sequencing (RNA-seq) data was collected and analyzed to investigate the synergistic mechanism of this combination. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways revealed by RNA-seq data analysis, a wound-healing assay was used to investigate the effect of this combination on the migration of MDA-MB-231 cells. Compared with treatment with 17-AAG or Belinostat alone, both the viability inhibition and apoptosis rate of MDA-MB-231 cells were significantly enhanced in the combination group. The combination index values were <1 in three concentration groups. Revealed by the RNA-seq data analysis, the most significantly enriched KEGG pathways in the combination group were closely associated with cell migration. Based on these findings, the anti-migration effect of this combination was investigated. It was revealed that the migration of MDA-MB-231 cells was significantly suppressed in the combination group compared with in the groups treated with 17-AAG or Belinostat alone. In terms of specific genes, the mRNA expression levels of TEA domain family proteins were significantly decreased in the combination group, whereas the phosphorylation of YY1 associated protein 1 and modulator of VRAC current 1 was significantly enhanced in the combination group. These alterations may help to explain the anti-migration effect of this combination. Belinostat has already been approved as a treatment for T-cell lymphoma and 17-AAG is undergoing clinical trials. These findings could provide a beneficial reference for the clinical treatment of patients with TNBC. D.A. Spandidos 2020-06 2020-03-26 /pmc/articles/PMC7160548/ /pubmed/32236631 http://dx.doi.org/10.3892/or.2020.7563 Text en Copyright: © Zuo et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zuo, Yu
Xu, Heng
Chen, Zhifeng
Xiong, Fengmin
Zhang, Bei
Chen, Kaixian
Jiang, Hualiang
Luo, Cheng
Zhang, Hao
17-AAG synergizes with Belinostat to exhibit a negative effect on the proliferation and invasion of MDA-MB-231 breast cancer cells
title 17-AAG synergizes with Belinostat to exhibit a negative effect on the proliferation and invasion of MDA-MB-231 breast cancer cells
title_full 17-AAG synergizes with Belinostat to exhibit a negative effect on the proliferation and invasion of MDA-MB-231 breast cancer cells
title_fullStr 17-AAG synergizes with Belinostat to exhibit a negative effect on the proliferation and invasion of MDA-MB-231 breast cancer cells
title_full_unstemmed 17-AAG synergizes with Belinostat to exhibit a negative effect on the proliferation and invasion of MDA-MB-231 breast cancer cells
title_short 17-AAG synergizes with Belinostat to exhibit a negative effect on the proliferation and invasion of MDA-MB-231 breast cancer cells
title_sort 17-aag synergizes with belinostat to exhibit a negative effect on the proliferation and invasion of mda-mb-231 breast cancer cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160548/
https://www.ncbi.nlm.nih.gov/pubmed/32236631
http://dx.doi.org/10.3892/or.2020.7563
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