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

被引：163

作者：

Nieth, C ^{[1
]}

Priebsch, A ^{[1
]}

Stege, A ^{[1
]}

Lage, H ^{[1
]}

机构：

[1] Humboldt Univ, Inst Pathol, Charite, D-10117 Berlin, Germany

来源：

FEBS LETTERS | 2003年 / 545卷 / 2-3期

关键词：

P-glycoprotein; MDR1; gastric cancer; pancreatic cancer; gene therapy;

D O I：

10.1016/S0014-5793(03)00523-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：144 / 150

页数：7

共 31 条

[1] P-glycoprotein is strongly expressed in the luminal membranes of the endothelium of blood vessels in the brain [J].

Beaulieu, E ;

Demeule, M ;

Ghitescu, L ;

Beliveau, R .

BIOCHEMICAL JOURNAL, 1997, 326 :539-544

[2]

BIEDLER JL, 1970, CANCER RES, V30, P1174

[3] A system for stable expression of short interfering RNAs in mammalian cells [J].

Brummelkamp, TR ;

Bernards, R ;

Agami, R .

SCIENCE, 2002, 296 (5567) :550-553

[4]

DIETEL M, 1990, CANCER RES, V50, P6100

[5] Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells [J].

Elbashir, SM ;

Harborth, J ;

Lendeckel, W ;

Yalcin, A ;

Weber, K ;

Tuschl, T .

NATURE, 2001, 411 (6836) :494-498

[6] Multidrug resistance in cancer: Role of ATP-dependent transporters [J].

Gottesman, MM ;

Fojo, T ;

Bates, SE .

NATURE REVIEWS CANCER, 2002, 2 (01) :48-58

[7] RNA interference [J].

Hannon, GJ .

NATURE, 2002, 418 (6894) :244-251

[8]

Harborth J, 2001, J CELL SCI, V114, P4557

[9]

Hatanaka H, 2001, ANTICANCER RES, V21, P879

[10] REVERSION OF MULTIDRUG-RESISTANCE IN THE P-GLYCOPROTEIN-POSITIVE HUMAN PANCREATIC-CELL LINE (EPP85-181RDB) BY INTRODUCTION OF A HAMMERHEAD RIBOZYME [J].

HOLM, PS ;

SCANLON, KJ ;

DIETEL, M .

BRITISH JOURNAL OF CANCER, 1994, 70 (02) :239-243

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