Mechanism of miR-126 Loaded in Albumin Nanoparticles for Reversing the Multidrug Resistance in Breast Carcinoma Cells

IF 2.9 4区 医学 Q1 Medicine
Yang Zhang, Yiming Yang, Ning Li, Fen Hu, Faming Tian, Hao Dai, Haifeng Cai, Jinyin Yan
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Abstract

This study discussed the mechanism of miR-126 loaded in albumin nanoparticles in reversing the multi drug resistance (MDR) in breast carcinoma cells through EGFR-MEK-ERK signal pathway. MCF-7/ADM cells were divided into blank set, empty vector set, miR-126 set and set of vector and miR-126 randomly. The change of drug susceptibility, protein expression of P-gp, BCRP, EGFR, p-EGFR, MEK, p-MEK, ERK and p-ERK, correlation between miR-126 and EGFR-MEK- ERK signal pathway were observed. miR-126 expression in set of vector was the highest. The second was in miR-126 set. IC50 of ADM in miR-126 set was 4.6 µg/mL. The reversion times were two times. The reversion times in set of vector and miR-126 set was 2.8 times. The presentation of BCRP and P-gp in miR-126 set and set of vector and miR-126 was reduced notably. The activity of EGFR-MEK-ERK signal pathway was restrained by miR-126. The content of p-EGFR, p-MEK and p-ERK in miR-126 set and set of vector and miR-126 was reduced notably compared with blank set. EGFR-MEK-ERK signal activity was targeting regulated by miR-126 loaded in albumin nanoparticles. The level of phosphoric acid activators was reduced abnormally. The expression of BCRP and P-gp was reduced notably. The MDR in breast carcinoma cells was reversed and the drug susceptibility was elevated notably.
载入白蛋白纳米颗粒的 miR-126 逆转乳腺癌细胞多药耐药性的机制
本研究探讨了载入白蛋白纳米颗粒的miR-126通过表皮生长因子受体-MEK-ERK信号通路逆转乳腺癌细胞多重耐药性(MDR)的机制。将 MCF-7/ADM 细胞随机分为空白组、空载体组、miR-126 组和载体与 miR-126 组。观察药物敏感性的变化、P-gp、BCRP、EGFR、p-EGFR、MEK、p-MEK、ERK 和 p-ERK 蛋白表达、miR-126 与 EGFR-MEK- ERK 信号通路的相关性。其次是 miR-126 组。miR-126 组中 ADM 的 IC50 为 4.6 µg/mL。逆转时间为两次。载体组和 miR-126 组的逆转时间为 2.8 倍。在 miR-126 组和载体与 miR-126 组中,BCRP 和 P-gp 的呈现明显减少。miR-126 抑制了表皮生长因子受体-MEK-ERK 信号通路的活性。与空白对照组相比,p-EGFR、p-MEK 和 p-ERK 在 miR-126 组和载体与 miR-126 组中的含量明显降低。载入白蛋白纳米颗粒的 miR-126 对表皮生长因子受体-MEK-ERK 信号活性具有靶向调节作用。磷酸激活剂的水平异常降低。BCRP 和 P-gp 的表达明显减少。乳腺癌细胞的 MDR 被逆转,对药物的敏感性显著提高。
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来源期刊
CiteScore
4.30
自引率
17.20%
发文量
145
审稿时长
2.3 months
期刊介绍: Information not localized
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