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Open AccessArticle

Drug Transporter Expression and Activity in Human Hepatoma HuH-7 Cells

Institut de Recherches en Santé, Environnement et Travail (IRSET), UMR INSERM U1085, Faculté de Pharmacie, 2 Avenue du Pr Léon Bernard, 35043 Rennes, France
Centre de Pharmacocinétique, Technologie Servier, 25–27 Rue Eugène Vignat, 45000 Orléans, France
Pôle Biologie, Centre Hospitalier Universitaire, 2 rue Henri le Guilloux, 35033 Rennes, France
Author to whom correspondence should be addressed.
Academic Editor: Yvonne Perrie
Pharmaceutics 2017, 9(1), 3;
Received: 3 November 2016 / Revised: 17 December 2016 / Accepted: 22 December 2016 / Published: 28 December 2016
Human hepatoma cells may represent a valuable alternative to the use of human hepatocytes for studying hepatic drug transporters, which is now a regulatory issue during drug development. In the present work, we have characterized hepatic drug transporter expression, activity and regulation in human hepatoma HuH-7 cells, in order to determine the potential relevance of these cells for drug transport assays. HuH-7 cells displayed notable multidrug resistance-associated protein (MRP) activity, presumed to reflect expression of various hepatic MRPs, including MRP2. By contrast, they failed to display functional activities of the uptake transporters sodium taurocholate co-transporting polypeptide (NTCP), organic anion-transporting polypeptides (OATPs) and organic cation transporter 1 (OCT1), and of the canalicular transporters P-glycoprotein and breast cancer resistance protein (BCRP). Concomitantly, mRNA expressions of various sinusoidal and canalicular hepatic drug transporters were not detected (NTCP, OATP1B1, organic anion transporter 2 (OAT2), OCT1 and bile salt export pump) or were found to be lower (OATP1B3, OATP2B1, multidrug and toxin extrusion protein 1, BCRP and MRP3) in hepatoma HuH-7 cells than those found in human hepatocytes, whereas other transporters such as OAT7, MRP4 and MRP5 were up-regulated. HuH-7 cells additionally exhibited farnesoid X receptor (FXR)- and nuclear factor erythroid 2-related factor 2 (Nrf2)-related up-regulation of some transporters. Such data indicate that HuH-7 cells, although expressing rather poorly some main hepatic drug transporters, may be useful for investigating interactions of drugs with MRPs, notably MRP2, and for studying FXR- or Nrf2-mediated gene regulation. View Full-Text
Keywords: hepatoma; hepatocytes; HuH-7; drug transporters; MRP2 hepatoma; hepatocytes; HuH-7; drug transporters; MRP2
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Jouan, E.; Le Vée, M.; Denizot, C.; Parmentier, Y.; Fardel, O. Drug Transporter Expression and Activity in Human Hepatoma HuH-7 Cells. Pharmaceutics 2017, 9, 3.

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