Analysis of drug transporter expression in human intestinal Caco-2 cells by real-time PCR

Fundam Clin Pharmacol. 2007 Dec;21(6):659-63. doi: 10.1111/j.1472-8206.2007.00550.x.

Abstract

Expression of drug transporters corresponds to a crucial parameter in intestinal Caco-2 cells widely used for investigating drug absorption. In order to characterize it in an accurate, reproducible and comparative manner, we analyzed mRNA levels of 19 influx and efflux drug transporters through real-time quantitative polymerase chain reaction assays combined with the use of a total RNA reference standard. Profiles of transporter expression were found to be significantly correlated in two independent Caco-2 cell clones and in human small intestine, which may support the use of Caco-2 cells for investigating intestinal drug transport. Several transporters were nevertheless quantitatively expressed at higher (MRP2, MRP3, MRP4, MRP5, MRP6, OATP-A, OATP-B, OCT1 and MCT1) or lower (BCRP) levels in Caco-2 cells comparatively to small intestine. Moreover, MDR1, MRP2, OATP-A and PEPT1 mRNA relative expression were found to differ in the two analyzed Caco-2 cell clones by at least a twofold factor, highlighting that some variations in transporter expression may occur in Caco-2 cells depending on cell origin, and therefore underlining the interest of carefully characterizing transporter levels in any Caco-2 cell clone before its use for drug transport assays.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Caco-2 Cells
  • Humans
  • Intestinal Mucosa / metabolism*
  • Membrane Transport Proteins / genetics*
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins / genetics
  • Organic Anion Transporters / genetics
  • RNA, Messenger / analysis
  • Reference Standards
  • Reverse Transcriptase Polymerase Chain Reaction / methods*

Substances

  • ABCB1 protein, human
  • ABCC2 protein, human
  • ABCC4 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • Organic Anion Transporters
  • RNA, Messenger
  • SLCO1A2 protein, human
  • multidrug resistance-associated protein 3
  • multidrug resistance-associated protein 1