Comparative Study of Culture Conditions for Maintaining CYP3A4 and ATP-Binding Cassette Transporters Activity in Primary Cultured Human Hepatocytes

DOI Web Site PubMed 被引用文献4件 参考文献60件
  • Takeba Yuko
    Department of Pharmacology, St. Marianna University School of Medicine, Japan
  • Matsumoto Naoki
    Department of Pharmacology, St. Marianna University School of Medicine, Japan
  • Takenoshita-Nakaya Sachiko
    Department of Pharmacology, St. Marianna University School of Medicine, Japan
  • Harimoto Yoshie
    Department of Pharmacology, St. Marianna University School of Medicine, Japan
  • Kumai Toshio
    Department of Pharmacogenomics, St. Marianna University School of Medicine, Japan
  • Kinoshita Yuichi
    Department of Pharmacology, St. Marianna University School of Medicine, Japan
  • Nakano Hiroshi
    Division of Gastroenterological Surgery, St. Marianna University School of Medicine, Japan
  • Ohtsubo Takehito
    Division of Gastroenterological Surgery, St. Marianna University School of Medicine, Japan
  • Kobayashi Shinichi
    Department of Pharmacology, St. Marianna University School of Medicine, Japan

この論文をさがす

抄録

The aim of this study was to determine suitable culture conditions for maintaining the activity of cytochrome p450 (CYP) 3A4 and drug transporters in primary cultured human hepatocytes. Human hepatocytes were isolated using the two-step collagenase perfusion technique and were cultured with four different media, serum-free William’s E medium (serum-free WEM), WEM containing fetal calf serum (FCS-WEM), WEM with human serum (HS-WEM), and Lanford’s medium. The albumin levels were maintained for 7 days in hepatocytes. Although CYP3A4 mRNA levels gradually decreased from 3 days, CYP3A4 and hepatocyte nuclear factor-4α alpha protein levels and activities were maintained for 7 days in hepatocytes cultured with serum-free WEM and Lanford’s but not in those with FCS-WEM and HS-WEM. Furthermore, CYP3A4 protein levels were significantly increased by the addition of rifampicin and dexamethasone to the culture media, indicating that the induction potential was maintained. The protein levels of P-glycoprotein, multi-drug-resistance-2, and breast cancer-resistance protein were maintained for 7 days in all media. Serum-free WEM and Lanford’s also maintained protein levels of CYP2C19, CYP2D6, and organic anion transporter polypeptide in the hepatocytes. Serum-free WEM and Lanford’s may be appropriate culture media for maintaining CYP3A4 and drug transporter protein levels in primary cultured hepatocytes.

収録刊行物

被引用文献 (4)*注記

もっと見る

参考文献 (60)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ