Relationship between expression level of P-glycoprotein and daunorubicin transport in LLC-PK1 cells transfected with human MDR1 gene

Kumiko Tanaka, Midori Hirai, Yusuke Tanigawara, Kazumitsu Ueda, Mikihisa Takano, Ryohei Hori, Ken Ichi Inui

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

P-Glycoprotein-mediated transcellular transport and intracellular accumulation of [3H]daunorubicin were examined in cell monolayers with different levels of P-glycoprotein. The porcine kidney epithelial cell line LLC-PK1 was transfected with MDR1 cDNA, and four sublines, LLC-GA5, LLC-GA5-VLB4, LLC-GA5-COL10, and LLC-GA5-COL150, were obtained by culturing the cells in the absence or in the presence of 4 ng/mL vinblastine, 10 ng/mL colchicine, and 150 ng/mL colchicine, respectively. Western blot analysis showed a large difference in P-glycoprotein expression within these sublines. The degree of drug resistance was dependent on the expression level of P-glycoprotein. The amount of the unidirectional transport of [3H]daunorubicin by P-glycoprotein corresponded to the expression level of P-glycoprotein, which was followed by the decrease in intracellular accumulation of the agent. The concentration of cyclosporin A required for the inhibition of P-glycoprotein-mediated transport of [3H]daunorubicin was higher in cells with a high expression of P-glycoprotein. These findings suggest that the transport of daunorubicin by P-glycoprotein and its inhibition by cyclosporin A correspond to the expression level of P-glycoprotein.

Original languageEnglish
Pages (from-to)741-746
Number of pages6
JournalBiochemical Pharmacology
Volume53
Issue number5
DOIs
Publication statusPublished - 1997 Mar 7
Externally publishedYes

Keywords

  • P-glycoprotein
  • cyclosporin A
  • daunorubicin
  • multidrug resistance
  • transcellular transport

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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