MDR1/P-glycoprotein (ABCB1) as target for RNA interference-mediated reversal of multidrug resistance.

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Lage H

MDR1/P-glycoprotein (ABCB1) as target for RNA interference-mediated reversal of multidrug resistance.

Curr Drug Targets. 2006 Jul;7(7):813-21.

PubMed ID

16842213 [ View in PubMed

]

Abstract

Resistance of tumor cells to multiple structurally unrelated cytotoxic drugs, multidrug resistance (MDR), is the major limitation to the successful chemotherapeutic treatment of disseminated neoplasms. The "classical" MDR phenotype is the result from decreased cellular drug accumulation mediated by the adenosine triphosphate binding cassette (ABC)-transporter MDR1/P-glycoprotein (MDR1/P-gp, ABCB1) encoded by the human MDR1 gene. Inhibition of the drug extrusion activity of MDR1/P-gp by low-molecular weight pharmacologically active compounds as a method to reverse MDR in patients suffering on malignant diseases has been studied capaciously, but the clinical results have generally been disappointing. Thus, experimental therapeutic strategies to reverse MDR are under extensive investigation. These strategies included gene therapeutic approaches with antisense oligonucleotides (ODNs), ribozymes, or DNAzymes and, most recently, the application of the RNA interference (RNAi) technology. RNAi is a physiological double stranded RNA-triggered mechanism resulting in gene-silencing in a sequence-specific manner. Transient RNAi can be attained by application of small interferring RNAs (siRNAs), whereas a stable RNAi-mediated gene-silencing can be achieved by transfection of mammalian cells with short hairpin RNA (shRNA) encoding expression cassettes localized on plasmid or viral vectors. Transient and stable RNAi strategies were applied to overcome MDR1/P-gp-mediated MDR in different in vitro models derived from various neoplastic tissue and will be come up for discussion.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
ATP	ATP-binding cassette sub-family G member 1	Protein	Humans	Unknown	Not Available	Details
ATP	P-glycoprotein 1	Protein	Humans	Unknown	Not Available	Details