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Title:
Enhanced autophagy reveals vulnerability of P-gp mediated epirubicin resistance in triple negative breast cancer cells | Apoptosis
Description:
Epirubicin (EPI) is widely used for triple negative breast cancer (TNBC), but a substantial number of patients develop EPI resistance that is associated with poor outcome. The underlying mechanism for EPI resistance remains poorly understood. We have developed and characterized an EPI-resistant (EPI-R) cell line from parental MDA-MB-231 cells. These EPI-R cells reached stable growth in the medium containing 8 μg/ml of EPI. They overexpressed P-glycoprotein (P-gp) and contained numerous autophagic vacuoles. The suppression of P-gp overexpression and/or autophagy restored the sensitivity of these EPI-R cells to EPI. We further show that autophagy conferred resistance to EPI on MDA cells by blocking the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated pro-apoptotic signals. Together, these results reveal a synergistic role of P-gp, autophagy, and NF-κB pathways in the development of EPI resistance in TNBC cells. They also suggest that blocking the P-gp overexpression and autophagy may be an effective means of reducing EPI resistance.
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Keywords {🔍}
pubmed, article, google, scholar, cancer, cas, autophagy, cell, cells, resistance, breast, central, pgp, wang, apoptosis, zhang, epi, min, line, nfκb, research, res, epirubicin, triple, negative, yang, liu, role, triplenegative, china, oncol, lanzhou, privacy, cookies, content, chen, pglycoprotein, development, access, gansu, university, publish, search, xie, dong, epir, mdamb, autophagic, death, drug,
Topics {✒️}
nuclear factor kappa-light-chain-enhancer nf-κb-dependent trail resistance beta-catenin/gsk-3beta modulation triple-negative breast cancer targeting nuclear factor-kappa increases pgp-mediated multidrug-resistance month download article/chapter nf-κb activity decreases mda-mb-231/epi cell line nf-κb signaling pathways cisplatin-resistant cell line parental mda-mb-231 cells mediated pro-apoptotic signals er stress-induced autophagy k562/a02 cell line doxorubicin-treated mcf-7 cells anti-malaria drug artesunate bortezomib-induced cell death cell-cycle-dependent turnover nf-κb pathways facilitates epirubicin-resistance development breast cancer resistance abc-cassette transporters mitochondrial apoptosis pathway gastric cancer cells full article pdf metastatic breast cancer related subjects epirubicin-induced apoptosis multidrug-resistant cells article apoptosis aims pancreatic cancer cells nf-κb monitoring autophagic flux innovative research team fundamental research funds privacy choices/manage cookies mdr-1/p-gp autophagic cell death reis-filho js autophagy conferred resistance p-gp overexpression laffitte m-cn mtagrfp-mwasabi-lc3 breast cancer nme2 reduces proliferation stimuli-dependent fashion li s article zhang reducing epi resistance
Questions {❓}
- Levine B, Yuan J (2005) Autophagy in cell death: an innocent convict?
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headline:Enhanced autophagy reveals vulnerability of P-gp mediated epirubicin resistance in triple negative breast cancer cells
description:Epirubicin (EPI) is widely used for triple negative breast cancer (TNBC), but a substantial number of patients develop EPI resistance that is associated with poor outcome. The underlying mechanism for EPI resistance remains poorly understood. We have developed and characterized an EPI-resistant (EPI-R) cell line from parental MDA-MB-231 cells. These EPI-R cells reached stable growth in the medium containing 8 μg/ml of EPI. They overexpressed P-glycoprotein (P-gp) and contained numerous autophagic vacuoles. The suppression of P-gp overexpression and/or autophagy restored the sensitivity of these EPI-R cells to EPI. We further show that autophagy conferred resistance to EPI on MDA cells by blocking the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated pro-apoptotic signals. Together, these results reveal a synergistic role of P-gp, autophagy, and NF-κB pathways in the development of EPI resistance in TNBC cells. They also suggest that blocking the P-gp overexpression and autophagy may be an effective means of reducing EPI resistance.
datePublished:2016-01-14T00:00:00Z
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Autophagy
P-gp
NF-κB
Epirubicin
Chemotherapy resistance
Triple negative breast cancer
Cancer Research
Cell Biology
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Biochemistry
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headline:Enhanced autophagy reveals vulnerability of P-gp mediated epirubicin resistance in triple negative breast cancer cells
description:Epirubicin (EPI) is widely used for triple negative breast cancer (TNBC), but a substantial number of patients develop EPI resistance that is associated with poor outcome. The underlying mechanism for EPI resistance remains poorly understood. We have developed and characterized an EPI-resistant (EPI-R) cell line from parental MDA-MB-231 cells. These EPI-R cells reached stable growth in the medium containing 8 μg/ml of EPI. They overexpressed P-glycoprotein (P-gp) and contained numerous autophagic vacuoles. The suppression of P-gp overexpression and/or autophagy restored the sensitivity of these EPI-R cells to EPI. We further show that autophagy conferred resistance to EPI on MDA cells by blocking the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated pro-apoptotic signals. Together, these results reveal a synergistic role of P-gp, autophagy, and NF-κB pathways in the development of EPI resistance in TNBC cells. They also suggest that blocking the P-gp overexpression and autophagy may be an effective means of reducing EPI resistance.
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P-gp
NF-κB
Epirubicin
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Triple negative breast cancer
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