PUBLICATION
Synergistic effects of A-B-C-type amphiphilic copolymer on reversal of drug resistance in MCF-7/ADR breast carcinoma
- Authors
- Zhang, L., Lu, J., Qiu, L.
- ID
- ZDB-PUB-161028-8
- Date
- 2016
- Source
- International Journal of Nanomedicine 11: 5205-5220 (Journal)
- Registered Authors
- Keywords
- P-glycoprotein, doxorubicin, micelle, multidrug resistance, zebrafish
- MeSH Terms
-
- Doxorubicin/chemistry
- Doxorubicin/pharmacology*
- Drug Resistance, Multiple/drug effects*
- Breast Neoplasms/drug therapy*
- Breast Neoplasms/pathology
- Polyethylene Glycols/chemistry
- ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism
- MCF-7 Cells
- Drug Resistance, Neoplasm/drug effects*
- Antibiotics, Antineoplastic/chemistry
- Antibiotics, Antineoplastic/pharmacology*
- Humans
- Animals
- Zebrafish/growth & development
- Zebrafish/metabolism
- Xenograft Model Antitumor Assays
- Apoptosis/drug effects
- Polymers/chemistry
- Polymers/pharmacology*
- Micelles
- Female
- beta-Cyclodextrins/chemistry
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- PubMed
- 27785023 Full text @ Int. J. Nanomedicine
Citation
Zhang, L., Lu, J., Qiu, L. (2016) Synergistic effects of A-B-C-type amphiphilic copolymer on reversal of drug resistance in MCF-7/ADR breast carcinoma. International Journal of Nanomedicine. 11:5205-5220.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping