| RRC ID |
55735
|
| 著者 |
Miyamoto R, Nozawa T, Shiozuka K, Tabata K.
|
| タイトル |
The Impact of Endogenous Breast Cancer Resistance Protein on Human P-Glycoprotein-Mediated Transport Assays Using LLC-PK1 Cells Transfected With Human P-Glycoprotein.
|
| ジャーナル |
J Pharm Sci
|
| Abstract |
Lilly Laboratories cell porcine kidney 1 (LLC-PK1) cells transfected with human P-glycoprotein (LLC-PK1-P-gp) are widely used in transport assays to identify drug candidates that function as substrates of this efflux transporter. Endogenous transporters expressed in LLC-PK1 cells may complicate the interpretation of findings from P-gp-mediated transport assays. We investigated the impact of porcine breast cancer resistance protein (Bcrp) in P-gp-mediated transport assays in LLC-PK1 cells. Porcine Bcrp mRNA was detected in both LLC-PK1 wildtype (WT) and LLC-PK1-P-gp cells by quantitative RT-PCR. To investigate the activity and impact of porcine Bcrp, we conducted transport assays using 6 typical BCRP substrates in LLC-PK1 cells. Efflux ratios (ER) of the 6 BCRP substrates in LLC-PK1 WT cells were >2, and were reduced in the presence of the BCRP inhibitor Ko143. The efflux activities of the 6 BCRP substrates were confirmed using MDCKII cells transfected with human BCRP. Net ERs of prazosin and fluvastatin, dual substrates of P-gp and BCRP, determined by dividing ERs in LLC-PK1-P-gp cells by those in LLC-PK1 WT cells, were <2, but increased to >2 in the presence of Ko143. These results indicated that endogenous Bcrp in LLC-PK1 cells was involved in the transport of BCRP substrates and may interfere with the identification of P-gp substrates.
|
| 巻・号 |
108(3)
|
| ページ |
1085-1089
|
| 公開日 |
2019-3-1
|
| DOI |
10.1016/j.xphs.2018.10.012
|
| PII |
S0022-3549(18)30612-9
|
| PMID |
30339864
|
| MeSH |
ATP Binding Cassette Transporter, Subfamily B / genetics
ATP Binding Cassette Transporter, Subfamily B / metabolism
ATP Binding Cassette Transporter, Subfamily G, Member 2 / antagonists & inhibitors
ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics
ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism*
Animals
Diketopiperazines / pharmacology
Drug Evaluation, Preclinical / methods*
Fluvastatin / pharmacology
Heterocyclic Compounds, 4 or More Rings / pharmacology
LLC-PK1 Cells
Prazosin / pharmacology
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Swine
Transfection
|
| IF |
3.197
|
| 引用数 |
0
|
| リソース情報 |
| ヒト・動物細胞 |
LLC-GA5-CoL150(RCB0871) |
