[1]胡晓磊,黄萍妹,王洁,等.MiR433 靶向调控Notch1 逆转人乳腺癌细胞对多西他赛的耐药性[J].南方医科大学学报,2018,(07):888.
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MiR433 靶向调控Notch1 逆转人乳腺癌细胞对多西他赛的耐药性()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2018年07期
页码:
888
栏目:
出版日期:
2018-06-30

文章信息/Info

Title:
MiR-433 reverses chemoresistance to docetaxel by targeting Notch1 in breast cancer cells
作者:
胡晓磊黄萍妹王洁何婉赵攀姚广裕叶长生
关键词:
多西他赛耐药性乳腺癌miR-433MCF-7Notch1
Keywords:
docetaxel chemoresistance breast cancer miR-433 MCF-7 Notch1
摘要:
目的探讨miR-433在多西他赛对乳腺癌耐药机制中的作用。方法将MCF-7乳腺癌细胞暴露于逐渐增强浓度的多西他 赛中建立对多西他赛耐药的乳腺癌细胞(MCF-7/DOX),并用miR-433 抑制剂及对照剂转染MCF-7/DOX细胞,采用酶标仪 (BioTek)测量吸光度和FACS流式细胞仪检测来评估miR-433的功能和作用;通过生物信息学分析、荧光素酶报告基因测定法 等技术确定miR-433的下游靶标。结果实时定量PCR结果显示miR-433在MCF-7/DOX细胞中的表达下调;细胞活力测定结 果表明miR-433抑制剂能促进产生多西他赛耐药,并减弱MCF-7细胞的凋亡,而miR-433过表达能增强多西他赛的敏感性并且 诱导MCF-7/DOX细胞凋亡。荧光素酶报告基因测定结果显示在miR-433表达显著下调的MCF-7细胞中,Notch1的mRNA和 蛋白质表达水平明显增强;miR-433mimics转染的MCF-7/DOX细胞与对照组(mimics-Ctrl)相比,Notch1的mRNA和蛋白表达 显着降低。结论miR-433可通过抑制Notch1的表达来逆转乳腺癌对多西他赛的耐药性,继续发挥药物的有效性。
Abstract:
Objective To investigate the role of miR- 433 in chemoresistance to docetaxel in breast cancer cells. Methods A docetaxel-resistant MCF-7 breast cancer cell line (MCF-7/DOX) was established by exposure of parental MCF-7 cells to progressively increased docetaxel concentrations. The functional role of miR-433 was investigated by assessing the changes in viability and apoptosis of the cells transfected with a miR-433 inhibitor or a miR-433 mimics. The downstream targets of miR- 433 were determined by bioinformatics analysis, cell transfection and luciferase reporter assay. Results Quantitative real-time PCR analysis showed that miR- 433 was down-regulated in MCF-7/DOX cells. Transfection of the cells with the miR-433 inhibitor obviously enhanced chemoresistance to docetaxel and attenuated cell apoptosis in MCF-7 cells; miR-433 overexpression significantly increased the sensitivity to docetaxel and promoted apoptosis in MCF- 7/DOX cells. Luciferase reporter assay showed that the down-regulation miR-433 expression was associated with significantly increased expressions of Notch1 at both mRNA and protein levels in MCF-7 cells. Compared with the control cells, McF-7/DOX cells transfected with miR-433 mimics exhibited significantly decreased mRNA and protein expressions of Notch1. Conclusions miR-433 may reverse chemoresistance to docetaxel by targeting Notch1 in breast cancer cells.

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更新日期/Last Update: 1900-01-01