| RRC ID |
39543
|
| Author |
Aiba T, Susa M, Fukumori S, Hashimoto Y.
|
| Title |
The effects of culture conditions on CYP3A4 and MDR1 mRNA induction by 1alpha,25-dihydroxyvitamin D(3) in human intestinal cell lines, Caco-2 and LS180.
|
| Journal |
Drug Metab Pharmacokinet
|
| Abstract |
To evaluate an in vitro model suitable for investigating intestinal first-pass drug metabolism, CYP3A4 and MDR1 mRNA induction by 1alpha,25-dihydroxyvitamin D(3) (VD3) was examined in two human intestinal cell lines, Caco-2 and LS180, under various culture conditions. CYP3A4 mRNA expression was induced by 100 nM VD3 at levels between 234-549 times above normal in Caco-2 cells for 2 weeks and by 74-200 times above normal in LS180 cells for 2 days. The CYP3A4 induction effect of 250 nM VD3 was similar to or slightly higher than that of 100 nM VD3 in both Caco-2 and LS180 cells. Also, CYP3A4 was induced in Caco-2 and LS180 cells when they were cultured on a polystyrene plate slightly less than when they were cultured on a porous membrane. The increase in fetal bovine serum (FBS) content in the culture medium resulted in little or only slight increase of CYP3A4 induction in both Caco-2 and LS180 cells. MDR1 mRNA expression was marginally increased by VD3 in LS180 cells, but not in Caco-2 cells, and neither increased FBS content nor use of a porous membrane significantly affected MDR1 induction in LS180 cells. The transepithelial electrical resistance of LS180 cells was almost zero, whereas that of Caco-2 cells was high and was marginally decreased by VD3. These findings indicate that Caco-2 cells cultured on a porous membrane with 100 nM VD3 for 2 weeks may be used as a model to investigate the intestinal absorption and first-pass metabolism of drugs, while LS180 cells may be utilized to elucidate the mechanisms which regulate intestinal CYP3A4 mRNA expression.
|
| Volume |
20(4)
|
| Pages |
268-74
|
| Published |
2005-8-1
|
| DOI |
10.2133/dmpk.20.268
|
| PII |
JST.JSTAGE/dmpk/20.268
|
| PMID |
16141606
|
| MeSH |
ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis*
ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
Caco-2 Cells
Calcitriol / pharmacology*
Cell Line
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System / biosynthesis*
Cytochrome P-450 Enzyme System / genetics
Enzyme Induction / drug effects
Humans
Intestines / drug effects
Intestines / enzymology
Models, Animal
RNA, Messenger / biosynthesis
Time Factors
|
| IF |
2.772
|
| Resource |
| Human and Animal Cells |
CACO-2(RCB0988) |
