Decreased expression of P-glycoprotein during differentiation in the human intestinal cell line Caco-2.

The expression profile of the multidrug resistance (MDR) 1 gene product P-glycoprotein (Pgp) was examined during culture using Caco-2 cells as an in vitro model. Levels of MDR1 and cyclooxygenase 2 mRNA expression in Caco-2 cells were the highest on day 3 and decreased with days in culture, but the level of cyclooxygenase 1 was stable throughout the culture period. The stability of MDR1 mRNA was 7-fold higher on day 3 than on day 9, and the run-on assay suggested the transcription rate of the MDR1 gene on day 3 tended to be higher than on day 9. In addition, the expression of Pgp was comparable with that of MDR1 mRNA, but was inversely correlated with villin expression. The Pgp-mediated tacrolimus transport was the highest on day 1 and the lowest on day 11. These results suggested that the changeable mRNA stability rather than transcription rate of MDR1 contributed to its up-regulation during cell proliferation and down-regulation after post-confluent differentiation in Caco-2 cells. Therefore, the temporal induction and subsequent down-regulation of the enterocyte Pgp could affect bioavailability of several drugs during the regeneration of the intestinal wall.