Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2.
Article Details
- CitationCopy to clipboard
Hooijberg JH, Broxterman HJ, Kool M, Assaraf YG, Peters GJ, Noordhuis P, Scheper RJ, Borst P, Pinedo HM, Jansen G
Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2.
Cancer Res. 1999 Jun 1;59(11):2532-5.
- PubMed ID
- 10363967 [ View in PubMed]
- Abstract
Transfection of multidrug resistance proteins (MRPs) MRP1 and MRP2 in human ovarian carcinoma 2008 cells conferred a marked level of resistance to short-term (1-4 h) exposure to the polyglutamatable antifolates methotrexate (MTX; 21-74-fold), ZD1694 (4-138-fold), and GW1843 (101-156-fold). Evidence for MRP-mediated antifolate efflux relies upon the following findings: (a) a 2-3.3-fold lower accumulation of [3H]MTX and subsequent reduced formation of long-chain polyglutamate forms of MTX; (b) reversal of MTX resistance by probenecid in both transfectants, and (c) ATP-dependent uptake of [3H]MTX in inside-out vesicles of MRP1 and MRP2 transfectants. This report provides a mechanistic basis for resistance to polyglutamatable antifolates through an MRP-mediated drug extrusion.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Methotrexate Canalicular multispecific organic anion transporter 1 Protein Humans UnknownSubstrateInhibitorDetails Probenecid Multidrug resistance-associated protein 1 Protein Humans UnknownInhibitorDetails