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Up-regulation of MDR1 function and expression by cisplatin in LLC-PK1 cells

Kohji Takara1, Masayuki Tsujimoto, Misato Kokufu

  • 1Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto, Japan. takara@mb.kyoto-phu.ac.jp

Biological & Pharmaceutical Bulletin
|February 11, 2003
PubMed

Insights

Cisplatin treatment increases multidrug resistance 1 (MDR1) expression and function in kidney cells. This suggests transient cisplatin exposure can up-regulate MDR1, potentially affecting drug efficacy.

Area of Science:

  • Nephrology
  • Pharmacology
  • Molecular Biology

Background:

  • The multidrug transporter MDR1/P-glycoprotein plays a crucial role in drug efflux from cells.
  • Understanding how chemotherapy agents like cisplatin interact with MDR1 in renal cells is vital for optimizing treatment outcomes.

Purpose of the Study:

  • To investigate the impact of cisplatin on the function and expression of MDR1 in kidney epithelial cells.
  • To determine if cisplatin exposure alters cellular sensitivity to MDR1 substrates.

Main Methods:

  • Utilized porcine kidney LLC-PK1 cells, which mimic renal proximal tubular cells.
  • Assessed cell sensitivity to paclitaxel, Rhodamine123 uptake/efflux, and MDR1 mRNA levels after cisplatin pretreatment.
  • Evaluated the effect of ciclosporin on Rhodamine123 efflux.

Main Results:

  • Cisplatin pretreatment shifted the paclitaxel growth inhibitory curve to higher concentrations.
  • Rhodamine123 uptake decreased, while efflux significantly increased post-cisplatin exposure.
  • Ciclosporin treatment reversed the enhanced Rhodamine123 efflux, confirming MDR1 involvement.
  • MDR1 mRNA expression levels were elevated by cisplatin exposure.

Conclusions:

  • Transient exposure to cisplatin leads to the up-regulation of MDR1 in LLC-PK1 cells.
  • Cisplatin's effect on MDR1 may influence the transport of other drugs within the kidneys.
  • Further research is warranted to explore the clinical implications of cisplatin-induced MDR1 modulation in renal drug transport.

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