Comparison of the expression and function of ATP binding cassette transporters in Caco-2 and T84 cells on stimulation by selected endogenous compounds and xenobiotics.
Caco-2 and T84 cells are intestinal epithelial model cells. Caco-2 cells are more commonly used in drug transport studies, whereas only a few studies have used T84 cells, and the two cell lines have not been compared. We cultured Caco-2 and T84 cells on plastic dishes or polycarbonate Transwell filters and compared the expression and function of ATP binding cassette (ABC) transporters, including multidrug resistance protein (MDR) 1 and multidrug resistance-associated protein (MRP) 2 and MRP3, in response to various compounds. Overall, the pattern of change in transporter mRNA expression in response to compounds was very similar regardless of culture conditions (plastic dish or polycarbonate filter) and cell line (Caco-2 or T84), and changes in MDR1 function was accompanied by expression changes. The cells cultured on Transwell filters were more sensitive to the tested compounds, regardless of the cell line. On comparing the two cell lines, the intrinsic function of MDR1 was stronger in Caco-2 cells, while sensitivity to the tested compounds was more prominent in T84 cells. These results suggest that Caco-2 cells are more suitable for identifying whether MDR1 mediates drug transport, while T84 cells are more useful for assessing the induction capacity of compounds.
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyoto, Japan. knaruhas@dwc.doshisha.ac.jp
Kazumasa
K
Naruhashi
Yuko
Y
Kurahashi
Yukari
Y
Fujita
Eri
E
Kawakita
Yuna
Y
Yamasaki
Kana
K
Hattori
Asako
A
Nishimura
Nobuhito
N
Shibata
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D001663:Bilirubin / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D018938:Caco-2 Cells / Q000187:drug effects / Q000378:metabolism; D020355:Cholates / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis*; D012313:RNA / Q000032:analysis; D013656:Taurocholic Acid / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D015262:Xenobiotics / Q000494:pharmacology
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001663:Bilirubin; D020355:Cholates; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012313:RNA; D013656:Taurocholic Acid; D015262:Xenobiotics; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C114462:multidrug resistance-associated protein 3