The down-regulation of SLC7A11 enhances ROS induced P-gp over-expression and drug resistance in MCF-7 breast cancer cells

Abstract Adriamycin (ADR) induces the over-expression of P-glycoprotein (P-gp) and multiple drug resistance in breast cancer cells. However, the biochemical process and underlying mechanisms are not clear. Our previous study revealed that ADR increased reactive oxygen species (ROS) generation and de...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Chun Ge, Bei Cao, Dong Feng, Fang Zhou, Jingwei Zhang, Na Yang, Siqi Feng, Guangji Wang, Jiye Aa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/13e5613b1d2141a3bc3ada2ae6cb0dbe
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:13e5613b1d2141a3bc3ada2ae6cb0dbe
record_format	dspace
spelling	oai:doaj.org-article:13e5613b1d2141a3bc3ada2ae6cb0dbe2021-12-02T15:04:59ZThe down-regulation of SLC7A11 enhances ROS induced P-gp over-expression and drug resistance in MCF-7 breast cancer cells10.1038/s41598-017-03881-92045-2322https://doaj.org/article/13e5613b1d2141a3bc3ada2ae6cb0dbe2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03881-9https://doaj.org/toc/2045-2322Abstract Adriamycin (ADR) induces the over-expression of P-glycoprotein (P-gp) and multiple drug resistance in breast cancer cells. However, the biochemical process and underlying mechanisms are not clear. Our previous study revealed that ADR increased reactive oxygen species (ROS) generation and decreased glutathione (GSH) biosynthesis, while N-acetylcysteine, the ROS scavenger, reversed the over-expression of P-gp. The present study showed that ADR inhibited the influx of cystine (the source material of GSH) and the activity of the SLC7A11 transporter (in charge of cystine uptake) in MCF-7 cells. For the first time, we showed that the down-regulation/silence of SLC7A11, or cystine deprivation, or enhanced ROS exposure significantly increased P-gp expression in MCF-7 cells. The down-regulation of SLC7A11 markedly enhanced ROS induced P-gp over-expression and drug resistance in MCF-7 cells; a combination of either an inhibited/silenced SLC7A11 or cystine deprivation and increased ROS dramatically promoted P-gp expression, which could be reversed by N-acetylcysteine. In contrast, the over-expression of SLC7A11, or supplementation with sufficiently cystine, or treatment with N-acetylcysteine significantly decreased P-gp expression and activity. It was suggested that ROS and SLC7A11/cystine were the two relevant factors responsible for the expression and function of P-gp, and that SLC7A11 might be a potential target modulating ADR resistance.Chun GeBei CaoDong FengFang ZhouJingwei ZhangNa YangSiqi FengGuangji WangJiye AaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chun Ge Bei Cao Dong Feng Fang Zhou Jingwei Zhang Na Yang Siqi Feng Guangji Wang Jiye Aa The down-regulation of SLC7A11 enhances ROS induced P-gp over-expression and drug resistance in MCF-7 breast cancer cells
description	Abstract Adriamycin (ADR) induces the over-expression of P-glycoprotein (P-gp) and multiple drug resistance in breast cancer cells. However, the biochemical process and underlying mechanisms are not clear. Our previous study revealed that ADR increased reactive oxygen species (ROS) generation and decreased glutathione (GSH) biosynthesis, while N-acetylcysteine, the ROS scavenger, reversed the over-expression of P-gp. The present study showed that ADR inhibited the influx of cystine (the source material of GSH) and the activity of the SLC7A11 transporter (in charge of cystine uptake) in MCF-7 cells. For the first time, we showed that the down-regulation/silence of SLC7A11, or cystine deprivation, or enhanced ROS exposure significantly increased P-gp expression in MCF-7 cells. The down-regulation of SLC7A11 markedly enhanced ROS induced P-gp over-expression and drug resistance in MCF-7 cells; a combination of either an inhibited/silenced SLC7A11 or cystine deprivation and increased ROS dramatically promoted P-gp expression, which could be reversed by N-acetylcysteine. In contrast, the over-expression of SLC7A11, or supplementation with sufficiently cystine, or treatment with N-acetylcysteine significantly decreased P-gp expression and activity. It was suggested that ROS and SLC7A11/cystine were the two relevant factors responsible for the expression and function of P-gp, and that SLC7A11 might be a potential target modulating ADR resistance.
format	article
author	Chun Ge Bei Cao Dong Feng Fang Zhou Jingwei Zhang Na Yang Siqi Feng Guangji Wang Jiye Aa
author_facet	Chun Ge Bei Cao Dong Feng Fang Zhou Jingwei Zhang Na Yang Siqi Feng Guangji Wang Jiye Aa
author_sort	Chun Ge
title	The down-regulation of SLC7A11 enhances ROS induced P-gp over-expression and drug resistance in MCF-7 breast cancer cells
title_short	The down-regulation of SLC7A11 enhances ROS induced P-gp over-expression and drug resistance in MCF-7 breast cancer cells
title_full	The down-regulation of SLC7A11 enhances ROS induced P-gp over-expression and drug resistance in MCF-7 breast cancer cells
title_fullStr	The down-regulation of SLC7A11 enhances ROS induced P-gp over-expression and drug resistance in MCF-7 breast cancer cells
title_full_unstemmed	The down-regulation of SLC7A11 enhances ROS induced P-gp over-expression and drug resistance in MCF-7 breast cancer cells
title_sort	down-regulation of slc7a11 enhances ros induced p-gp over-expression and drug resistance in mcf-7 breast cancer cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/13e5613b1d2141a3bc3ada2ae6cb0dbe
work_keys_str_mv	AT chunge thedownregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells AT beicao thedownregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells AT dongfeng thedownregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells AT fangzhou thedownregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells AT jingweizhang thedownregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells AT nayang thedownregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells AT siqifeng thedownregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells AT guangjiwang thedownregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells AT jiyeaa thedownregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells AT chunge downregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells AT beicao downregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells AT dongfeng downregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells AT fangzhou downregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells AT jingweizhang downregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells AT nayang downregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells AT siqifeng downregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells AT guangjiwang downregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells AT jiyeaa downregulationofslc7a11enhancesrosinducedpgpoverexpressionanddrugresistanceinmcf7breastcancercells
_version_	1718388938054303744

The down-regulation of SLC7A11 enhances ROS induced P-gp over-expression and drug resistance in MCF-7 breast cancer cells

Ejemplares similares