Influence of IL-6 on MDR and MRP-mediated multidrug resistance in human hepatoma cells

Can J Physiol Pharmacol. 2001 Oct;79(10):876-84.


The objective of this study was to examine effects of interleukin-6 (IL-6) on the expression and activity of the drug resistance transporters (MDR1 and MRP) in human hepatoma cell lines. Expression and activity of MDR1 and MRP transporters were examined in IL-6-treated and control HuH 7 and HepG2 cells using semi-quantitative RT-PCR analysis and by rhodamine 123 and 5-carboxyfluorescin efflux assays. Results from RT-PCR demonstrated expression of MRP3, MRP6, and MDR1 in HuH 7 cells and expression of MRP1, MRP2, MRP3, MRP6, and MDR1 in HepG2 cells. Compared with controls, treatment of HuH 7 cells with IL-6 (10 ng/mL, 24 h) resulted in a 1.8-fold increase in MRP-mediated efflux of 5-CF with a corresponding 1.5-fold induction of MRP3 mRNA levels (p < 0.05). Similarly, in HepG2 cells, a 2-fold increase in MRP functional activity and a 1.8-fold induction of MRP1 mRNA levels were seen in the IL-6 treated cells (p < 0.05). Treatment of cells with IL-6 was also found to cause significant reductions in the expression and activity of MDR1 in HuH 7 cells, but not in HepG2 cells. Our data suggest that IL-6 induces MRP expression and activity in human hepatoma cell lines. Suppressive effects of IL-6 on MDR1 expression and activity were also observed in HuH 7 cells. This underscores the importance of examining the regulation of multiple drug resistance proteins as these proteins may have opposing regulatory mechanisms in malignant cells.

MeSH terms

  • Blood Proteins / metabolism
  • Blotting, Western
  • Carcinoma, Hepatocellular / metabolism*
  • Cytokines / metabolism
  • Drug Resistance, Multiple / genetics
  • Drug Resistance, Multiple / physiology*
  • Drug Resistance, Neoplasm / genetics
  • Drug Resistance, Neoplasm / physiology*
  • Fluoresceins
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genes, MDR / genetics
  • Genes, MDR / physiology*
  • Humans
  • Interleukin-6 / pharmacology*
  • Liver Neoplasms / metabolism*
  • RNA, Messenger / biosynthesis
  • Radioisotopes
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhodium
  • Tumor Cells, Cultured


  • Blood Proteins
  • Cytokines
  • Fluoresceins
  • Interleukin-6
  • RNA, Messenger
  • Radioisotopes
  • 4-carboxyfluorescein
  • Rhodium