Multidrug resistance-associated protein - reduction of expression in humanleukaemia cells by antisense phosphorothioate olignucleotides

Multidrug resistance-associated protein (MRP1) causes cellular drug resista nce in several cancer cell lines. In this paper we show that antisense olig onucleotides decrease MRP1 expression in human leukaemia cells. We investig ated biological activity of a series of 12 linear phosphorothioate oligonuc leotides, complementary to several regions of MRP1 mRNA. The oligonucleotid es were administered to leukaemia HL60/ADR cells overexpressing MRP1 protei n. Then, the level of MRP1 mRNA was determined by means of semiquantitative RT-PCR and the protein level by reaction with specific monoclonal antibodi es. Some of the investigated antisense oligonucleotides decrease the expres sion level of the MRP1 protein by 46% and its mRNA level by 76%.