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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
Polymers for Advanced Technologies ( IF 3.1 ) Pub Date : 2020-03-24 , DOI: 10.1002/pat.4906
Safura Pakizehkar 1 , Najmeh Ranji 1 , Alireza Naderi Sohi 2 , Majid Sadeghizadeh 3
Affiliation  

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 by in silico approaches, 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 as P53, CASP9 and BAX after 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.

中文翻译:

姜黄素负载的PEG400-OA纳米颗粒:一种合适的系统,可在MDA-MB-231人乳腺癌细胞中增加凋亡,减少迁移并调节miR-125b / miR182

姜黄素是一种抗癌药,但其低溶解度限制了其临床应用。miRNA的失控与其靶标之间的关系表明,miRNA可能是姜黄素在治疗不同癌症中的重要靶标。在这项研究中,为了克服这种黄金药物临床使用的本质缺陷,开发了姜黄素包裹的聚合物小颗粒(CPN),并研究了其对MDA-MB-231乳腺癌细胞的细胞毒性作用。与miR-182 / 125b中的表达水平和在细胞凋亡途径的一些潜在目标中的表达模式,通过预测在硅片通过RT-qPCR对CPNs处理和未处理的细胞进行了分析。此外,通过蛋白质印迹法确定CASP9和CASP8蛋白的量。通过刮擦试验研究了CPNs对细胞迁移的影响,并通过Western印迹法检测了CPNs处理和未处理的细胞中EGFR,E-钙粘着蛋白和β-连环蛋白的水平。RT-qPCR分析确定了CPNs处理的细胞中miR-125b和miR-182的下调以及某些预测的凋亡靶基因(如P53,CASP9BAX)的上调24小时后。蛋白质印迹证实姜黄素对裂解的CASP9蛋白的增加有影响。根据当前实验的数据,经过CPNs处理后,MDA-MB-231细胞的迁移减少了。根据结果​​,CPNs作为合适且兼容的纳米载体,可以更有效地将姜黄素递送到癌细胞中,并且可以部分地通过抑制miR-125b和miR-182以及增加姜黄素对MDA-MB-231细胞的治疗作用。诱导细胞凋亡并抑制转移进程。
更新日期:2020-03-24
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