Multidrug resistance inhibition by antisense oligonucleotide against MDR1/mRNA in P-glycoprotein expressing leukemic cells

Abstract Introduction: Acute myeloblastic leukemia (AML) is the most common form of acute leukemia in adults. One major problem in this disease is the emergence of leukemic blast cells that are resistant to anticancer drugs. This phenomenon is termed multidrug resistance (MDR). One cause of MDR is the expression of the MDR1 gene and its product, P-glycoprotein (Pgp). Aim: In the present study, we tried to inhibit the MDR phenotype with MDR1/mRNA/Pgp in leukemic cells using different antisense sequences and two non-viral vectors. Materials and methods: The Pgp expressing cell line was established from a parental K562 (Erythroleukemia) cell line with increasing concentrations of doxorubicin, and named KDI/20. In order to reverse the MDR phenotype due to Pgp expression, four different sequences of sense, antisense and one random sequence with phosphorothioate (PTO) modification (PS-ODN) against MDR1/mRNA were synthesized. They were used on the KDI/20 cells in combination with two non-viral vectors: (1) Fugen...