Characterization of multidrug transporters in a normal renal tubular cell line resistant to doxorubicin. Multidrug transporters in the LLC-PK(1) cell line and its resistant counterpart.

Abstract:

:LLC-PK(1) is a proximal tubular cell line derived from normal pig kidney which has a structure and function similar to those of renal proximal tubular cells and which expresses baseline levels of P-glycoprotein. We isolated by drug selection a doxorubicin-resistant cell line (LLC-PK(1)/ADR) that exhibited a multidrug-resistant phenotype; this cell line was characterized by reduced intracellular drug concentrations, an increased drug extrusion, and increased expression of a 170-kDa P-glycoprotein detected by Western blot analysis with monoclonal antibody C219. In addition, an increased expression of MDR1 mRNA was seen by reverse transcriptase-polymerase chain reaction. These results suggest that it is possible to induce the overexpression of P-glycoprotein by chronic treatment with doxorubicin in a normal cell line that physiologically expresses low levels of this protein. This multi-resistant cell line could provide an interesting model for studying the role of P-glycoprotein and the consequence of its induction in a normal tissue.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Decorti G,Rosati A,Candussio L,Giraldi T,Bartoli Klugmann F

doi

10.1016/s0006-2952(00)00535-9

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

61-6

issue

1

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(00)00535-9

journal_volume

61

pub_type

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