Modulation of the classical multidrug resistance (MDR) phenotype by RNA interference (RNAi)

Modulation of the classical multidrug resistance (MDR) phenotype by RNA interference (RNAi)
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DOI:
10.1016/s0014-5793(03)00523-4
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发表时间:
2003-06-19
期刊:
影响因子:
3.5
通讯作者:
Lage, H
Lage, H
中科院分区:
生物学3区
文献类型:
--
作者:
Nieth, C;Priebsch, A;Lage, H

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为了逆转MDR 1基因依赖的多药耐药(MDR),设计了两种小干扰RNA(siRNA)构建体,通过RNA干扰来抑制MDR 1表达。用siRNA双链体处理人胰腺癌(EPP 85 - 181 RDB)和胃癌(EPG 85 - 257 RDB)细胞。在这两种细胞系统中,siRNA可以特异性地抑制MDR 1在mRNA和蛋白水平上的表达高达91%。对柔红霉素的耐药性降低至89%(EPP 85 - 181 RDB)或58%(EPG 85 - 257 RDB)。这些数据表明,这种方法可能适用于癌症患者作为一种特定的手段,以扭转肿瘤与P-糖蛋白依赖性MDR表型回到药物敏感的。(C)2003年欧洲生物化学学会联合会。由Elsevier Science B. V.出版,版权所有。
For reversal of MDR1 gene-dependent multidrug resistance (MDR), two small interfering RNA (siRNA) constructs were designed to inhibit MDR1 expression by RNA interference. SiRNA duplexes were used to treat human pancreatic carcinoma (EPP85-181RDB) and gastric carcinoma (EPG85-257RDB) cells. In both cellular systems, siRNAs could specifically inhibit MDR1 expression up to 91% at the mRNA and protein levels. Resistance against daunorubicin was decreased to 89% (EPP85-181RDB) or 58% (EPG85-257RDB). The data indicate that this approach may be applicable to cancer patients as a specific means to reverse tumors with a P-glycoprotein-dependent MDR phenotype back to a drug-sensitive one. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.