Induction of Human P-Glycoprotein in Caco-2 cells: Development of a Highly Sensitive Assay System for P-Glycoprotein-Mediated Drug Transport
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- SHIRASAKA Yoshiyuki
- Faculty of Pharmaceutical Sciences, Setsunan University
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- KAWASAKI Masae
- Faculty of Pharmaceutical Sciences, Setsunan University
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- SAKANE Toshiyasu
- Faculty of Pharmaceutical Sciences, Setsunan University
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- OMATSU Hideaki
- Department of Hospital Pharmacy, School of Medicine, Kobe University
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- MORIYA Yuka
- Department of Hospital Pharmacy, School of Medicine, Kobe University
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- NAKAMURA Tsutomu
- Department of Hospital Pharmacy, School of Medicine, Kobe University
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- SAKAEDA Toshiyuki
- Department of Hospital Pharmacy, School of Medicine, Kobe University
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- OKUMURA Katsuhiko
- Department of Hospital Pharmacy, School of Medicine, Kobe University
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- LANGGUTH Peter
- School of Pharmacy, Johannes Gutenberg-University
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- YAMASHITA Shinji
- Faculty of Pharmaceutical Sciences, Setsunan University
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Abstract
The aim of this work is to develop a highly sensitive assay system for P-gp-mediated transport by using two methods, induction of P-gp and short-term culture of Caco-2 cells. To induce P-gp in Caco-2 cells, cells were cultured in vinblastine-containing medium. The mRNA level of P-gp was approximately 7-fold higher in Caco-2 cells cultured with vinblastine (P-gp-induced Caco-2 cells) than in control cells. Western blot analysis showed a significant increase in P-gp expression. After cell differentiation, the mRNA level of P-gp was downregulated, however, P-gp-induced Caco-2 cells still possessed a 5.6-fold higher mRNA level of P-gp compared to control cells. Polarized transport of substrate drugs was greater in the monolayer of P-gp-induced cells than in that of control cells. Moreover, we found that P-gp expression in Caco-2 cells could be further enhanced by applying the higher concentration of vinblastine. Transport activity of P-gp in Caco-2 cells cultured with higher concentration of vinblastine was markedly higher than that in P-gp-induced Caco-2 cells and was comparable with that in MDR1-MDCKII cells. In conclusion, this study provided a stable and highly sensitive in vitro assay system that can identify compounds that are subject to P-gp-mediated efflux.<br>
Journal
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- Drug Metabolism and Pharmacokinetics
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Drug Metabolism and Pharmacokinetics 21 (5), 414-423, 2006
The Japanese Society for the Study of Xenobiotics
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Details 詳細情報について
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- CRID
- 1390282680156375552
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- NII Article ID
- 10018307102
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- NII Book ID
- AA1162652X
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- COI
- 1:CAS:528:DC%2BD28XhtlWnsr7F
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- ISSN
- 18800920
- 13474367
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- PubMed
- 17072095
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- Text Lang
- en
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- Data Source
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- JaLC
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed