Reference - Detail
| RRC ID | 55735 |
|---|---|
| Author | Miyamoto R, Nozawa T, Shiozuka K, Tabata K. |
| Title | The Impact of Endogenous Breast Cancer Resistance Protein on Human P-Glycoprotein-Mediated Transport Assays Using LLC-PK1 Cells Transfected With Human P-Glycoprotein. |
| Journal | 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. |
| Volume | 108(3) |
| Pages | 1085-1089 |
| Published | 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 |
| Times Cited | 0 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | LLC-GA5-CoL150(RCB0871) |