Encapsulation in lipid-core nanocapsules overcomes lung cancer cell resistance to tretinoin

被引：33
|
作者：
Schultze, Eduarda [1 ]
Ourique, Aline [2 ]
Yurgel, Virginia Campello [1 ]
Begnini, Karine Rech [1 ]
Thurow, Helena [1 ]
Moura de Leon, Priscila Marques [1 ]
Campos, Vinicius Farias [1 ]
Dellagostin, Odir Antonio [1 ]
Guterres, Silvia R. [2 ]
Pohlmann, Adriana R. [2 ,3 ]
Seixas, Fabiana Koemmling [1 ]
Beck, Ruy Carlos Ruver [2 ]
Collares, Tiago [1 ]
机构：
[1] Univ Fed Pelotas, Biotecnol Ctr Desenvolvimento Tecnol, Programa Posgrad Biotecnol PPGB, Grp Pesquisa Oncol Celular & Mol, Pelotas, Brazil
[2] Univ Fed Rio Grande do Sul, Fac Farm, BR-90610000 Porto Alegre, RS, Brazil
[3] Univ Fed Rio Grande do Sul, Inst Quim, Dept Quim Organ, BR-90610000 Porto Alegre, RS, Brazil
来源：
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS | 2014年 / 87卷 / 01期
关键词：
Tretinoin; Apoptosis; Nanocapsules; p21; Antitumor activity; Nanobiotechnology; TRANS-RETINOIC ACID; ACUTE PROMYELOCYTIC LEUKEMIA; TUMOR DRUG-RESISTANCE; PHASE-I TRIAL; RECEPTOR-BETA; STEM-CELLS; DIFFERENTIATION; PROLIFERATION; ATRA; CARCINOGENESIS;
D O I：
10.1016/j.ejpb.2014.02.003
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Tretinoin is a retinoid derivative that has an antiproliferative effect on several kinds of tumours. Human lung adenocarcinoma epithelial cell lines (A549) exhibit a profound resistance to the effects of tretinoin. Nanocarriers seem to be a good alternative to overcome cellular resistance to drugs. The aim of this study was to test whether tretinoin-loaded lipid-core nanocapsules exert an antitumor effect on A549 cells. A549 cells were incubated with free tretinoin (UN), blank nanocapsules (LNC) and tretinoin-loaded lipid-core nanocapsules (UN-LNC). Data from evaluation of DNA content and Annexin V binding assay by flow cytometry showed that TTN-LNC induced apoptosis and cell cycle arrest at the G1-phase while UN did not. UN-LNC showed higher cytotoxic effects than ITN on A549 cells evaluated by MTT and LIVE/DEAD cell viability assay. Gene expression profiling identified up-regulated expression of gene p21 by TTN-LNC, supporting the cell cycle arrest effect. These results showed for the first time that UN-LNC are able to overcome the resistance of adenocarcinoma cell line A549 to treatment with UN by inducing apoptosis and cell cycle arrest, providing support for their use in applications in lung cancer therapy. (C) 2014 Elsevier B.V. All rights reserved.
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收藏
页码：55 / 63
页数：9
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