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Gambogic acid-loaded pH-sensitive mixed micelles for overcoming breast cancer resistance
Wang S.; Yang Y.; Wang Y.; Chen M.
2015
Source PublicationInternational Journal of Pharmaceutics
Volume495Issue:2Pages:840
Abstract

Multidrug resistance (MDR) is one of the major obstacles to the successful treatment of breast cancer. The overexpression of drug efflux transporters such as P-glycoprotein (P-gp) and of anti-apoptotic proteins like survivin are the major causes of MDR. Here, we developed a gambogic acid (GA)-loaded mixed micelle system made of poly(ethylene glycol)-poly(l-histidine)-poly(d,l-lactide-co-glycolide) (PEG-pHis-PLGA) and d-α-tocopheryl polyethylene glycol 1000 (TPGS) that is potentially useful for overcoming MDR by integrating the beneficial effects of pH-sensitive behavior, P-gp inhibition, and down-regulation of anti-apoptotic proteins. The therapeutic potential and mechanism of action of GA-loaded pH-sensitive mixed micelles were examined in drug-sensitive human breast MCF-7 and drug-resistant MCF-7/ADR cells. The resulting GA-loaded mixed micelles with an average size of 190.1 nm were stable at pH 7.4, but dissociated rapidly in a weakly acidic environment (pH 5.5). The GA-loaded mixed micelles increased the cell cytotoxicity against both MCF-7 and MCF-7/ADR cells, which was associated with enhanced apoptosis. In addition, the GA-loaded mixed micelles down-regulated the expression of the anti-apoptotic proteins survivin and Bcl-2, and inhibited the expression and activity of P-gp in MCF-7/ADR cells. Our results indicate that this system could overcome drug resistant in breast cancer by targeting distinct mechanisms, which may facilitate the translation of the GA-mediated effects into clinical benefits. © 2015 Elsevier B.V. All rights reserved.

KeywordAnti-apoptotic Proteins Breast Cancer Gambogic Acid P-glycoprotein Ph-sensitive Mixed Micelles
DOI10.1016/j.ijpharm.2015.09.041
URLView the original
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000364124100024
The Source to ArticleScopus
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Cited Times [WOS]:24   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau999078, Macau
2.Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macau
Recommended Citation
GB/T 7714
Wang S.,Yang Y.,Wang Y.,et al. Gambogic acid-loaded pH-sensitive mixed micelles for overcoming breast cancer resistance[J]. International Journal of Pharmaceutics,2015,495(2):840.
APA Wang S.,Yang Y.,Wang Y.,&Chen M..(2015).Gambogic acid-loaded pH-sensitive mixed micelles for overcoming breast cancer resistance.International Journal of Pharmaceutics,495(2),840.
MLA Wang S.,et al."Gambogic acid-loaded pH-sensitive mixed micelles for overcoming breast cancer resistance".International Journal of Pharmaceutics 495.2(2015):840.
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