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Pharmazie ; 67(1): 86-90, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22393837

RESUMO

The kinetics of drug transport across the trophoblast layer is determined by several factors. Human choriocarcinoma cell lines like BeWo and JEG-3 have been used as models of the trophoblast layer to examine the placental transport of drugs. Previously, the drugs examined in these models have been readily transported across the trophoblast layer via cellular gap junctions. These backgrounds enabled us to establish the differentiating JEG-3 cell (DJEG) layer model, which suppresses paracellular drug transport, as an evaluation system of placental drug transport. The efflux transporters on the trophoblast layer assume the meaningful role of protecting the fetus from xenobiotic substances. In order to clarify the usefulness of our DJEG placental drug transport model, this study examined the mRNA expression profiles of the efflux transporters MRPs, MDR1, and BCRP in JEG-3 cells and compared them with those of BeWo cells and their known placental expression. We suggest that the mRNA of efflux transporters MRP 1-8 and BCRP are expressed widely in JEG-3 cells; however, expression levels of MDR1 mRNA were undetectable. It was also indicated that polymorphisms of BCRP C421A in both the BeWo and JEG-3 cells are of the wild-type. We demonstrated the efflux transporters' expression profiles, as well as those of the BeWo cells, was demonstrated in the DJEG placental drug transport evaluating model as well as the BeWo cells, in the DJEG placental drug transport evaluation model. Based on these findings, we hope that the DJEG model will be adequate for use in evaluating placental drug transport in relation to the transporter proteins.


Assuntos
Coriocarcinoma/metabolismo , Proteínas de Membrana Transportadoras/biossíntese , Proteínas de Membrana Transportadoras/genética , Preparações Farmacêuticas/metabolismo , Placenta/metabolismo , RNA Mensageiro/biossíntese , Neoplasias Uterinas/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/metabolismo , Transporte Biológico Ativo , Células CACO-2 , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Coriocarcinoma/genética , Claudina-1 , Primers do DNA , Feminino , Humanos , Proteínas de Membrana/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas de Neoplasias/metabolismo , Polimorfismo Genético/genética , Gravidez , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Junções Íntimas/metabolismo , Neoplasias Uterinas/genética
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