title: Vitamin E derivative-based multifunctional nanoemulsions for overcoming multidrug resistance in cancer.
abstract: The multidrug resistance (MDR), including intrinsic and acquired multidrug resistance, is a major problem in tumor chemotherapy. Here, we proposed a strategy for modulating intrinsic and/or acquired multidrug resistance by altering the levels of Bax and Bcl-2 expression and inhibiting the transport function of P-gp, increasing the intracellular concentration of its substrate anticancer drugs. Vitamin E derivative-based nanoemulsions containing paclitaxel (MNEs-PTX) were fabricated in this study, and in vitro anticancer efficacy of the nanoemulsion system was evaluated in the paclitaxel-resistant human ovarian carcinoma cell line A2780/Taxol. The MNEs-PTX exhibited a remarkably enhanced antiproliferation effect on A2780/Taxol cells than free paclitaxel (PTX) (p < 0.01). Compared with that in the Taxol group, MNEs-PTX further decreased mitochondrial potential. Vitamin E derivative-based multifunctional nanoemulsion (MNEs) obviously increased intracellular accumulation of rhodamine 123 (P-gp substrate). Overexpression of Bcl-2 is generally associated with tumor drug resistance, we found that MNEs could reduce Bcl-2 protein level and increase Bax protein level. Taken together, our findings suggest that anticancer drugs associated with MNEs could play a role in the development of MDR in cancers.
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy, Harbin Medical University , Harbin, PR China ;
authors.forename: Nannan
authors.initials: N
authors.lastname: Zheng
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy, Harbin Medical University , Harbin, PR China ;
authors.forename: Yanan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: b Department of Pharmacy, the Second Affiliated Hospital, Harbin Medical University , Harbin, PR China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Ji
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy, Harbin Medical University , Harbin, PR China ;|b Department of Pharmacy, the Second Affiliated Hospital, Harbin Medical University , Harbin, PR China.
authors.forename: Linhua
authors.initials: L
authors.lastname: Wu
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy, Harbin Medical University , Harbin, PR China ;
authors.forename: Xuejing
authors.initials: X
authors.lastname: Qi
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy, Harbin Medical University , Harbin, PR China ;
authors.forename: Xiaona
authors.initials: X
authors.lastname: Liu
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy, Harbin Medical University , Harbin, PR China ;
authors.forename: Jingling
authors.initials: J
authors.lastname: Tang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004655:Emulsions; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D049329:Nanostructures / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D010316:Particle Size; D013499:Surface Properties; D014810:Vitamin E / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004655:Emulsions; D014810:Vitamin E; D017239:Paclitaxel
keywords: Bcl-2 family proteins; P-glycoprotein; multidrug resistance; paclitaxel; vitamin E derivative-based multifunctional nanoemulsion