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Synergistic effects of A-B-C-type amphiphilic copolymer on reversal of drug resistance in MCF-7/ADR breast carcinoma
P-glycoprotein (P-gp) overexpression has become the most common cause of occurrence of multidrug resistance in clinical settings. We aimed to construct a micellar polymer carrier to sensitize drug-resistant tumors to doxorubicin (DOX). This A-B-C-type amphiphilic copolymer was prepared by the sequen...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066852/ https://www.ncbi.nlm.nih.gov/pubmed/27785023 http://dx.doi.org/10.2147/IJN.S115956 |
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author | Zhang, Lu Lu, Jiafei Qiu, Liyan |
author_facet | Zhang, Lu Lu, Jiafei Qiu, Liyan |
author_sort | Zhang, Lu |
collection | PubMed |
description | P-glycoprotein (P-gp) overexpression has become the most common cause of occurrence of multidrug resistance in clinical settings. We aimed to construct a micellar polymer carrier to sensitize drug-resistant tumors to doxorubicin (DOX). This A-B-C-type amphiphilic copolymer was prepared by the sequential linkage of β-cyclodextrin, hydrophobic poly(d,l-lactide), and hydrophilic poly(ethylene glycol). Upon incubation of the DOX-loaded micelles with DOX-resistant human breast carcinoma MCF-7/ADR cells, significantly enhanced cytotoxicity and apoptosis were achieved. A series of studies on the action mechanism showed that the polymer components such as β-cyclodextrin, hydrophobic poly(d,l-lactide) segment, and poly(ethylene glycol) coordinatively contributed to the improved intracellular ATP depletion and ATPase activity, increased intracellular uptake of P-gp substrates via competitive binding to P-gp, and decreased P-gp expression in MCF-7/ADR cells. More interestingly, a similar phenomenon was observed in the zebrafish xenograft model, resulting in ~64% inhibition of MCF-7/ADR tumor growth. These results implied that the polymeric micelles displayed great potentials as P-gp modulators to reverse DOX resistance in MCF-7/ADR breast carcinoma. |
format | Online Article Text |
id | pubmed-5066852 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-50668522016-10-26 Synergistic effects of A-B-C-type amphiphilic copolymer on reversal of drug resistance in MCF-7/ADR breast carcinoma Zhang, Lu Lu, Jiafei Qiu, Liyan Int J Nanomedicine Original Research P-glycoprotein (P-gp) overexpression has become the most common cause of occurrence of multidrug resistance in clinical settings. We aimed to construct a micellar polymer carrier to sensitize drug-resistant tumors to doxorubicin (DOX). This A-B-C-type amphiphilic copolymer was prepared by the sequential linkage of β-cyclodextrin, hydrophobic poly(d,l-lactide), and hydrophilic poly(ethylene glycol). Upon incubation of the DOX-loaded micelles with DOX-resistant human breast carcinoma MCF-7/ADR cells, significantly enhanced cytotoxicity and apoptosis were achieved. A series of studies on the action mechanism showed that the polymer components such as β-cyclodextrin, hydrophobic poly(d,l-lactide) segment, and poly(ethylene glycol) coordinatively contributed to the improved intracellular ATP depletion and ATPase activity, increased intracellular uptake of P-gp substrates via competitive binding to P-gp, and decreased P-gp expression in MCF-7/ADR cells. More interestingly, a similar phenomenon was observed in the zebrafish xenograft model, resulting in ~64% inhibition of MCF-7/ADR tumor growth. These results implied that the polymeric micelles displayed great potentials as P-gp modulators to reverse DOX resistance in MCF-7/ADR breast carcinoma. Dove Medical Press 2016-10-11 /pmc/articles/PMC5066852/ /pubmed/27785023 http://dx.doi.org/10.2147/IJN.S115956 Text en © 2016 Zhang et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Zhang, Lu Lu, Jiafei Qiu, Liyan Synergistic effects of A-B-C-type amphiphilic copolymer on reversal of drug resistance in MCF-7/ADR breast carcinoma |
title | Synergistic effects of A-B-C-type amphiphilic copolymer on reversal of drug resistance in MCF-7/ADR breast carcinoma |
title_full | Synergistic effects of A-B-C-type amphiphilic copolymer on reversal of drug resistance in MCF-7/ADR breast carcinoma |
title_fullStr | Synergistic effects of A-B-C-type amphiphilic copolymer on reversal of drug resistance in MCF-7/ADR breast carcinoma |
title_full_unstemmed | Synergistic effects of A-B-C-type amphiphilic copolymer on reversal of drug resistance in MCF-7/ADR breast carcinoma |
title_short | Synergistic effects of A-B-C-type amphiphilic copolymer on reversal of drug resistance in MCF-7/ADR breast carcinoma |
title_sort | synergistic effects of a-b-c-type amphiphilic copolymer on reversal of drug resistance in mcf-7/adr breast carcinoma |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066852/ https://www.ncbi.nlm.nih.gov/pubmed/27785023 http://dx.doi.org/10.2147/IJN.S115956 |
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