In vitro and in vivo reversal of MDR1-mediated multidrug resistance by KT-5720: implications on hematological malignancies.

Multidrug resistance (MDR) due to over-expression of the MDR1 (ABCB1) gene and its P-glycoprotein (Pgp) product is an obstacle in the treatment of hematological malignancies. In this study, we have evaluated the potency of KT-5720 to reverse Pgp-dependent MDR in vitro and in vivo. KT-5720 (but not its close derivatives, K252a and K252b) reversed multidrug resistance of LM1/MDR cell line at non-toxic concentrations and increased accumulation of rhodamine 123 (Rh123).

Establishment and characterization of new cellular lymphoma model expressing transgenic human MDR1.

Multidrug resistance (MDR) due to the expression of the MDR1 gene and its P-glycoprotein (Pgp) product is a major factor in the prognosis and clinical outcome of patients with refractory lymphomas and other malignancies. The aim of our study was to establish a lymphoma, cellular system where a de novo acquisition of multidrug resistance is specifically related to overexpression of a transgenic, human MDR1. A multidrug sensitive lymphoma cell line (LM1) was established from a sporadic T-cell lymphoma of BALB/c mouse and was transduced by a retroviral vector containing the human MDR1 cDNA.