Digoxin up-regulates MDR1 in human colon carcinoma Caco-2 cells

Biochem Biophys Res Commun. 2002 Mar 22;292(1):190-4. doi: 10.1006/bbrc.2002.6619.


Because MDR1 (P-glycoprotein) plays an important role in pharmacokinetics such as absorption and excretion of xenobiotics and multidrug resistance, an understanding of the factors regulating its function and expression is important. Here, the effects of digoxin on cell sensitivity to an anticancer drug, MDR1 function, and expression were examined by assessing the growth inhibition by paclitaxel, the transport characteristics of the MDR1 substrate Rhodamine123, and the level of MDR1 mRNA, respectively, using human colon carcinoma Caco-2 cells, which are widely used as a model of intestinal epithelial cells. The sensitivity to paclitaxel, an MDR1 substrate, in Caco-2 cells pretreated with digoxin was lower than that in non-treated cells. The accumulation of Rhodamine123 was reduced by pretreatment with digoxin and its efflux was enhanced. The level of MDR1 mRNA in Caco-2 cells was increased in a digoxin concentration-dependent manner. These results taken together suggested that digoxin up-regulates MDR1 in Caco-2 cells.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Antineoplastic Agents, Phytogenic / toxicity
  • Biological Transport
  • Caco-2 Cells
  • Cell Division / drug effects
  • Digoxin / pharmacology*
  • Dose-Response Relationship, Drug
  • Fluorescent Dyes / metabolism
  • Humans
  • Inhibitory Concentration 50
  • Kinetics
  • Paclitaxel / toxicity
  • RNA, Messenger / biosynthesis
  • Rhodamine 123 / metabolism
  • Up-Regulation*


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents, Phytogenic
  • Fluorescent Dyes
  • RNA, Messenger
  • Rhodamine 123
  • Digoxin
  • Paclitaxel