P-131 - γ-H2AX, CYP3A and CYP2J2 overexpression in a drug-resistant acute myeloid leukemia cell line

Abstract

Drug resistance is a major clinical problem in cancer treatment. Thus, it is important to establish cell line models to better understand and counteract this problem. The aim of this study was to establish and characterize a drug resistant acute myeloid leukemia cell line, as a sub-clone from a drug sensitive parental cell line. The resistant cell line (HL60–734 VR) was established by treating the parental sensitive cell line (HL60) with increasing concentrations of doxorubicin during several months. Dose-response curves were performed to confirm that the HL60–734 VR cell line was resistant to doxorubicin and to three other drugs (etoposide, cisplatin and daunorubicin). The resistant phenotype was not lost upon drug removal for 1 month. Resistant cells did not express the drug efflux pumps P-gp or BCRP, neither had alterations in apoptotic proteins such as Bax, XIAP, p53, Caspase-3 and Bcl-2. Resistant cells showed alterations in cell cycle profile and presented increased expression of a DNA repair protein (γ-H2AX) and also of proteins involved in drug metabolism (CYP3A and CYP2J2), suggesting that these alterations might be associated with the drug resistant phenotype in these cells.