Expression and activity of the efflux transporters ABCB1, ABCC2 and ABCG2 in the human colorectal carcinoma cell line LS513. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] Journal article | | Title | Expression and activity of the efflux transporters ABCB1, ABCC2 and ABCG2 in the human colorectal carcinoma cell line LS513. | | Author(s) | Salphati L, Plise EG, Li G | | Institution | Drug Metabolism and Pharmacokinetics Department, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States. salphati.laurent@gene.com | | Source | Eur J Pharm Sci 2009 Jun 28; 37(3-4):463-8. | | Abstract | The human colorectal carcinoma cell line LS513 exhibits epithelial morphology, adherent properties and can grow subcutaneously to form tumors in nude mice. Thus, it is a potential model for mouse xenograft efficacy studies. The present study characterized the expression and activity of P-gp, BCRP and MRP2 in LS513 cells. We investigated the expression of these ATP-binding cassette transporters by Western blot and their activity was also examined using cell culture inserts, where the LS513 cells were grown to confluence for 9 days. The transport of model substrates of P-gp (amprenavir, ritonavir and topotecan), BCRP (topotecan) and MRP2 (SN-38) was studied in the apical to basolateral (A-B) and basolateral to apical (B-A) directions. P-gp, BCRP and MRP2 could be detected by western blot. The LS513 cells exhibited markedly higher transport in the B-A direction than in the A-B direction for the probe substrates tested, with efflux ratios (ERs; B-A/A-B) of 10, 21, 40 and 50 for amprenavir, ritonavir, topotecan and SN38, respectively. The ER could be significantly reduced with the addition of inhibitors of P-gp (GF120918), BCRP (FTC), and MRP2 (MK571), confirming the activity of these transporters in the LS513 cells. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 19491037 |
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