Curcumin loaded PEG400-OA nanoparticles: A suitable system to increase apoptosis, decrease migration, and deregulate miR-125b/miR182 in MDA-MB-231 human breast cancer cells

被引:13
|
作者
Pakizehkar, Safura [1 ]
Ranji, Najmeh [1 ]
Naderi Sohi, Alireza [2 ]
Sadeghizadeh, Majid [3 ]
机构
[1] Islamic Azad Univ, Fac Sci, Dept Biol, Rasht Branch, POB 41235-3516, Rasht, Iran
[2] Stem Cell Technol Res Ctr, Dept Nanotechnol & Tissue Engn, Tehran, Iran
[3] Tarbiat Modares Univ, Sch Biol Sci, Dept Genet, Tehran, Iran
关键词
breast cancer; Curcumin; miR-125b; miR-182; polymersomes; IN-VITRO; CYCLE ARREST; EXPRESSION; MICRORNA; PROLIFERATION; MICELLES; DESIGN; DRUG;
D O I
10.1002/pat.4906
中图分类号
O63 [高分子化学(高聚物)];
学科分类号
070305 ; 080501 ; 081704 ;
摘要
Curcumin is an anti-cancerous agent, but its low-solubility limits its clinical use. The relationship between deregulation of miRNAs and their targets suggested that miRNAs can be interest targets of curcumin in treatment of different cancers. In this study, to overcome essential defects of the clinical usage of this golden drug, curcumin-encapsulated polymersome nanoparticles (CPNs) have been developed, and the cytotoxicity effects were studied on MDA-MB-231 breast cancer cells. The expression level of miR-182/125b and the expression pattern of some potential targets in apoptotic pathway, predicted byin silicoapproaches, were analyzed by RT-qPCR in CPNs-treated and untreated cells. Moreover, the amount of CASP9 and CASP8 proteins were determined by Western blotting. The effect of CPNs on cell migration were studied by scratch test and the level of EGFR, E-cadherin, and beta-catenin proteins were monitored in CPNs-treated and untreated cells by western blotting. RT-qPCR analysis identified the downregulation of miR-125b and miR-182 in CPNs-treated cells and the upregulation of some predicted apoptotic target genes such asP53, CASP9andBAXafter 24 hours. Western blotting confirmed the effects of curcumin on the increase of cleaved CASP9 protein. Based on data from the current experiment, the migration of MDA-MB-231 cells was decreased after CPNs treatment. According to the results, CPNs, as suitable and compatible nanocarriers, can deliver curcumin into cancerous cells more effectively and can increase the therapeutic effects of curcumin on MDA-MB-231 cells partly by suppression of miR-125b and miR-182 as well as induction of apoptosis and inhibition of metastatic progression.
引用
收藏
页码:1793 / 1804
页数:12
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