Digoxin up-regulates multidrug resistance transporter (MDR1) mRNA and simultaneously down-regulates steroid xenobiotic receptor mRNA

Biochem Biophys Res Commun. 2003 Jun 20;306(1):116-20. doi: 10.1016/s0006-291x(03)00922-7.


A steroid xenobiotic receptor (SXR) is involved in the induction of MDR1/P-glycoprotein. MDR1 up-regulation by digoxin was previously demonstrated in human colon adenocarcinoma Caco-2 cells, but the participation of SXR remains unclear. Herein, the participation of SXR in MDR1 up-regulation was examined using reverse transcription-polymerase chain reaction in Caco-2 cells, and digoxin-tolerant cells (Caco/DX) as well as human colon carcinoma LS180 cells, which expressed SXR. MDR1 mRNA expression in Caco-2 or LS180 cells was increased by exposure to 1 microM digoxin for 24h, in a concentration-dependent manner, but SXR mRNA decreased concentration-dependently and was undetectable or significantly lower at 1 microM digoxin, indicating antithetical changes in MDR1 and SXR mRNA expression. Moreover, the MDR1 mRNA level was higher in Caco/DX cells than Caco-2 cells, whereas the SXR mRNA level was lower in Caco/DX cells. Consequently, digoxin was demonstrated to up-regulate MDR1 mRNA and simultaneously down-regulate SXR mRNA expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Caco-2 Cells
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Digoxin / pharmacology*
  • Down-Regulation / drug effects
  • Genes, MDR / drug effects*
  • Humans
  • Pregnane X Receptor
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Receptors, Steroid / genetics*
  • Tumor Cells, Cultured
  • Up-Regulation / drug effects


  • Pregnane X Receptor
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Steroid
  • Digoxin