In vivo model systems in P-glycoprotein-mediated multidrug resistance

Wim Van De Vrie, Richard L. Marquet, Gerrit Stoter, Ernst A. De Bruijn, Alexander M.M. Eggermont

Onderzoeksoutput: Bijdrage aan tijdschriftArtikel recenserenpeer review

40 Citaten (Scopus)


In this article we review the in vivo model systems that have been developed for studying P-glycoprotein-mediated multidrug resistance (MDR) in the preclinical setting. Rodents have two mdr genes, both of which confer the MDR phenotype: mdr1a and mdr1b. At gene level they show strong homology to the human MDR1 gene and the tissue distribution of their gene product is very similar to P-glycoprotein expression in humans. In vivo studies have shown the physiological roles of P-glycoprotein, including protection of the organism from damage by xenobiotics. Tumors with intrinsic P-glycoprotein expression, induced MDR or transfected with an mdr gene, can be used as syngeneic or xenogenic tumor models. Ascites, leukemia, and solid MDR tumor models have been developed. Molecular engineering has resulted in transgenic mice that express the human MDR1 gene in their bone marrow and in knockout mice missing a murine mdr gene. The data on pharmacokinetics, efficacy, and toxicity of chemosensitizers of P-glycoprotein in vivo are described. Results from studies using monoclonal antibodies directed against P-glycoprotein and other miscellaneous approaches for modulation of MDR are mentioned. The importance of in vivo studies prior to clinical trials is being stressed and potential pitfalls due to differences between species are discussed.

Originele taal-2Engels
Pagina's (van-tot)1-57
Aantal pagina's57
TijdschriftCritical Reviews in Clinical Laboratory Sciences
Nummer van het tijdschrift1
StatusGepubliceerd - 1998
Extern gepubliceerdJa


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