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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Absorption properties and P-glycoprotein activity of modified Caco-2 cell lines.

Caco-2 cell line is extensively used as an in vitro model in studying small intestinal absorption but it lacks proper expression of efflux pumps and cytochrome P450 enzymes that are involved in absorption and first pass metabolism of drugs. We created two novel Caco-2 cell lines expressing orphan nuclear receptors pregnane X receptor and constitutive androstane receptor that regulate many genes involved in xenobiotic metabolism. We conducted a systematic study on expression of some metabolic genes, P-glycoprotein activity and absorption properties of several drugs with these new cell lines and previously described modified Caco-2 cell lines (MDR1 transfection, vincristine treatment and 1alpha,25-dihydroxyvitamin D3 treatment). A short culture time medium was also included in the study. Most modified cell lines formed tight differentiated monolayers. MDR1, CYP2C9 and CYP3A4 genes were upregulated in some cell lines. Elevated P-glycoprotein activities were observed by calcein-AM uptake experiments but this did not affect significantly the permeability of selected P-glycoprotein substrates. Some cell lines had similar passive and active permeability properties to Caco/WT cells while in few cell lines these were altered. Passive transcellular permeability was modestly elevated in all modified cell lines. In addition, several compounds showed pH-dependent permeability properties.[1]


  1. Absorption properties and P-glycoprotein activity of modified Caco-2 cell lines. Korjamo, T., Honkakoski, P., Toppinen, M.R., Niva, S., Reinisalo, M., Palmgrén, J.J., Mönkkönen, J. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. (2005) [Pubmed]
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