Gene expression profiles of ABC transporters and cytochrome P450 3A in Caco-2 and human colorectal cancer cell lines.

Purpose: The mRNA levels of MDR1 (P-glycoprotein), multidrug resistance-associated proteins (MRP1, MRP2), cytochrome P450 3A (CYP3A) and villin in human colorectal cell lines (HCT-15, LoVo DLD-1, HCT-116 and SW620) were quantitatively compared with those in Caco-2 cells.
Methods: The mRNA levels were determined by real time quantitative polymerase chain reaction and expressed as the relative concen trations of MDR1 mRNA to glyceraldehyde-3-phosphate dehydro genase (GAPDH) mRNA. RESULTSl MDR1 mRNA was expressed in HCT-15 LoVo and DLD-1 cells at similar or lower level to Caco-2. The expression of MRP mRNA in the cell lines tested was comparable with Caco-2. MRP. mRNA was detected only in HCT-116 and SW620 at significantly lower level than Caco-2. CYP3A mRNA was detected in HCT-15 LoVo, DLD-1 and SW620 at similar level to Caco-2.
Conclusions: HCT-15 LoVo and DLD-1 cells express proteins important for regulating the intestinal absorption of drugs, i.e., MDR1 MRP1 and CYP3A, whereas HCT-116 and SW620 cells were not acceptable for evaluation of absorption properties of drug candidates