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Silencing of ETS1 reverses adriamycin resistance in MCF-7/ADR cells via downregulation of MDR1

BACKGROUND: Clinical resistance to chemotherapeutic agents is one of the major hindrances in the treatment of human cancers. Erythroblastosis virus E26 oncogene homolog 1 (ETS1) is involved in the drug resistance of various cancer cells, and is overexpressed in drug-resistant human breast cancer cel...

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Autores principales: Wei, Jinrong, Zhou, Yong, Jiang, Guo-Qin, Xiao, Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995875/
https://www.ncbi.nlm.nih.gov/pubmed/24602286
http://dx.doi.org/10.1186/1475-2867-14-22
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author Wei, Jinrong
Zhou, Yong
Jiang, Guo-Qin
Xiao, Dong
author_facet Wei, Jinrong
Zhou, Yong
Jiang, Guo-Qin
Xiao, Dong
author_sort Wei, Jinrong
collection PubMed
description BACKGROUND: Clinical resistance to chemotherapeutic agents is one of the major hindrances in the treatment of human cancers. Erythroblastosis virus E26 oncogene homolog 1 (ETS1) is involved in the drug resistance of various cancer cells, and is overexpressed in drug-resistant human breast cancer cell lines. In this study, we investigated the effects of ETS1 on adriamycin resistance in MCF-7/ADR cells. METHODS: siRNAs against ETS1 or negative control siRNAs was transfected to MCF-7/ADR breast cancer cells. Reverse transcription-PCR and Western blotting were used to determine the mRNA and protein expression of ETS1 and MDR1. The cytotoxicity of adriamycin was assessed using the MTT assay. Drug efflux was investigated by flow cytometry using the Rhodamine 123 intracellular accumulation assay. RESULTS: ETS1 mRNA and protein was significantly overexpressed in MCF-7/ADR cells, compared to MCF-7 cells. ETS1 siRNA successfully silenced ETS1 mRNA and protein expression. Silencing of ETS1 also significantly reduced the mRNA and protein expression levels of MDR1 (multidrug resistance 1; also known as ABCB1, P-glycoprotein/P-gp), which is a major ATP-binding cassette (ABC) transporter linked to multi-drug resistance in cancer cells. Silencing of ETS1 significantly increased the sensitivity of MCF-7/ADR cells to adriamycin, compared to cells transfected with negative control siRNA. In addition, intracellular accumulation of Rhodamine 123 significantly increased in MCF-7/ADR cells transfected with ETS1 siRNA, indicating that silencing of ETS1 may reduce drug efflux. CONCLUSIONS: This study demonstrates that drug resistance can be effectively reversed in adriamycin-resistant breast carcinoma cells through delivery of siRNAs targeting ETS1.
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spelling pubmed-39958752014-04-23 Silencing of ETS1 reverses adriamycin resistance in MCF-7/ADR cells via downregulation of MDR1 Wei, Jinrong Zhou, Yong Jiang, Guo-Qin Xiao, Dong Cancer Cell Int Primary Research BACKGROUND: Clinical resistance to chemotherapeutic agents is one of the major hindrances in the treatment of human cancers. Erythroblastosis virus E26 oncogene homolog 1 (ETS1) is involved in the drug resistance of various cancer cells, and is overexpressed in drug-resistant human breast cancer cell lines. In this study, we investigated the effects of ETS1 on adriamycin resistance in MCF-7/ADR cells. METHODS: siRNAs against ETS1 or negative control siRNAs was transfected to MCF-7/ADR breast cancer cells. Reverse transcription-PCR and Western blotting were used to determine the mRNA and protein expression of ETS1 and MDR1. The cytotoxicity of adriamycin was assessed using the MTT assay. Drug efflux was investigated by flow cytometry using the Rhodamine 123 intracellular accumulation assay. RESULTS: ETS1 mRNA and protein was significantly overexpressed in MCF-7/ADR cells, compared to MCF-7 cells. ETS1 siRNA successfully silenced ETS1 mRNA and protein expression. Silencing of ETS1 also significantly reduced the mRNA and protein expression levels of MDR1 (multidrug resistance 1; also known as ABCB1, P-glycoprotein/P-gp), which is a major ATP-binding cassette (ABC) transporter linked to multi-drug resistance in cancer cells. Silencing of ETS1 significantly increased the sensitivity of MCF-7/ADR cells to adriamycin, compared to cells transfected with negative control siRNA. In addition, intracellular accumulation of Rhodamine 123 significantly increased in MCF-7/ADR cells transfected with ETS1 siRNA, indicating that silencing of ETS1 may reduce drug efflux. CONCLUSIONS: This study demonstrates that drug resistance can be effectively reversed in adriamycin-resistant breast carcinoma cells through delivery of siRNAs targeting ETS1. BioMed Central 2014-03-07 /pmc/articles/PMC3995875/ /pubmed/24602286 http://dx.doi.org/10.1186/1475-2867-14-22 Text en Copyright © 2014 Wei et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
spellingShingle Primary Research
Wei, Jinrong
Zhou, Yong
Jiang, Guo-Qin
Xiao, Dong
Silencing of ETS1 reverses adriamycin resistance in MCF-7/ADR cells via downregulation of MDR1
title Silencing of ETS1 reverses adriamycin resistance in MCF-7/ADR cells via downregulation of MDR1
title_full Silencing of ETS1 reverses adriamycin resistance in MCF-7/ADR cells via downregulation of MDR1
title_fullStr Silencing of ETS1 reverses adriamycin resistance in MCF-7/ADR cells via downregulation of MDR1
title_full_unstemmed Silencing of ETS1 reverses adriamycin resistance in MCF-7/ADR cells via downregulation of MDR1
title_short Silencing of ETS1 reverses adriamycin resistance in MCF-7/ADR cells via downregulation of MDR1
title_sort silencing of ets1 reverses adriamycin resistance in mcf-7/adr cells via downregulation of mdr1
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995875/
https://www.ncbi.nlm.nih.gov/pubmed/24602286
http://dx.doi.org/10.1186/1475-2867-14-22
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