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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
PURPOSE: We have isolated etoposide-resistant prostatic cancercell lines, P/VP10 and P/VP20, to investigate the multidrug resistance (MDR) mechanism and to find MDR reversal agents. MATERIALS AND METHODS: We examined expression of MDR-related genes and screened reversal agents of MDR in P/VP20 cells. RESULTS: These cells demonstrated a non-P-glycoprotein (P-gp)- mediated MDRphenotype with overexpression of MDR- associated protein ( MRP) mRNA due to MRP DNA amplification. A 1,4-dihydropyridine derivative, bis(4-pyridylmethyl)4-[2-(3-methyl-5,6- dihydro-1,4-dithiinyl)]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicar boxylate (NIK250), was found to overcome MDR in P/VP20 cells. CONCLUSIONS: NIK250 might be useful in reversing MDR, which often develops during chemotherapy of advanced or hormone-resistant prostatic cancer.[1]