Document Detail


The NCI-N87 cell line as a gastric epithelial barrier model for drug permeability assay.
MedLine Citation:
PMID:  21821011     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The objective of this study was to evaluate the human NCI-N87 cell line as a model for gastric permeability drug studies under pH conditions of the stomach. The optimal conditions that led NCI-N87 cells to form a typical differentiated gastric epithelial barrier were a seeding density of 2.5×10(5)cells/cm(2) on porous inserts and growth in serum-complemented RPMI-1640 medium until 18-27days post-confluency. The resulting cell monolayers showed moderately high transepithelial electrical resistance values of about 500Ωcm(2), cells of polygonal morphology expressing E-cadherin and ZO-1 proteins at their contact surfaces, and production of mucus clusters. The monolayers withstood apical pH of 7.4 down to 3.0 with the basal pH fixed at 7.4. The apparent permeability coefficients (P(app)) of model compounds were evaluated in the basolateral-to-apical and apical-to-basolateral directions under different pH gradients. The monolayers were impermeable to the integrity marker Lucifer Yellow (low P(app) of 0.3-1.1×10(-6)cm/s). The furosemide P(app) (0.4-1.5×10(-5)cm/s) were slightly dependent on pH but remained moderate. The caffeine P(app) (4.2-5.0×10(-5)cm/s) were higher and insensitive to pH changes. The NCI-N87 cell line provides a useful in vitro tool to assess gastric drug permeability and absorption under physiologic conditions prevailing in the human stomach.
Authors:
Marc Lemieux; Frédéric Bouchard; Patrick Gosselin; Joanne Paquin; Mircea Alexandru Mateescu
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-29
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  -     ISSN:  1090-2104     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-8-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Inc.
Affiliation:
Department of Chemistry-Biochemistry and Centre Pharmaqam, Université du Québec à Montréal, CP 8888, Succ. Centre-ville, Montréal (Québec), Canada H3C 3P8.
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