Expression of multi drug resistance (MDR1) gene in human promyelocytic leukemia cell line selected with vincristine

MDR1 mediated drug resistance is one of the main problems for some cancer chemotherapies. Vincristine (VCR) is an effective drug used in clinical treatment of acute leukemias. The concentration of VCR was stepwise increased (1-50 nM) in the cell culture media of HL60 cells (AML cell line). The viability of cells was determined and the expression of MDR1 gene was studied by using reverse transcriptasepolymerase chain reaction (RT-PCR). In sensitive HL60 cells MDR1 gene expression was not present. The level of the MDR1 gene expression increased in cells with stepwise increases of VCR concentration. MDR1 gene expression was about six times more in 50 nM VCR resistant cells than in 2 nM VCR applied HL60 cells. The IC50 values in sensitive and resistant HL60 cells were 4 nM and 300 nM, respectively. The results indicated that HL60/VCR cells were 75-fold more resistant to vincristine compared to sensitive HL60 cells. It was observed that the cells that were resistant to high concentrations of VCR express MDR1 gene at high levels.[Turk J Cancer 2005;35(2):88-92]. INTRODUCTION Chemotherapy has been very effective in the treatment of non-localized cancers. However, upon relapse many cancers become resistant to further chemotherapy, even with drugs that have not been previously used. This phenomenon is termed as multidrug resistance (MDR). The mechanisms underlying this clinical phenomenon have been studied using in vitro models, leading to characterization of genes capable of conferring resistance to chemotherapeutic drugs. Different mechanisms have been characterized in MDR (1). One of the mechanisms that is known to contribute to this phenomenon is the expression of the ATP-dependent P-glycoprotein. P-glycoprotein is included in a large super family of transport proteins termed, ATP Binding Cassette (ABC) transporters or traffic ATPases (2). Among these genes, multidrug resistance gene (MDR1) has been of particular interest because its overexpression can lead to resistance to drugs such as anthracyclines, vinca alkaloids and podophyllins, which are important in the treatment of leukemia (3). MDR1 gene, located on chromosome 7, encodes for a 170-kDa glycoprotein (P-gp). The broad spectrum of drugs affected by MDR1 has made it an attractive candidate to explain the phenomenon of clinical resistance, whereby leukemia cells or tumor becomes refractory to drugs to which it has never been exposed (4). YUSUF BARAN1, UFUK GÜNDÜZ1, AL‹ U⁄UR URAL2 1Middle East Technical University, Department of Biological Sciences, Ankara, 2Gülhane Military Medical Academy, Department of Hematology, Ankara-Turkey