Investigation of the role of LRP in multidrug resistance

摘要: There have been many reports linking the overexpression of lung resistance-related protein (LRP) with cross-resistance to chemotherapeutic drugs. However, no conclusive evidence existed link LRP a direct role in multidrug resistance (LRP). The OAW42SR is cell line derived from serous adenocarcinoma ovaries, and displays an increase cytotoxic drugs concomitant moderate expression. Anti- ribozyme antisense expression plasmids were employed this study order inhibit examine any resulting effect on drug cells. Antisense oligonucleotides also used decrease provide clearer picture whether involved MDR. A large number clones isolated after transfection anti- plasmids. These displayed varying levels at both mRNA level. Cells transfected only control vector decreases expression, highlighting extent clonal variation within population. anti-LRP construct appeared significantly reduce RNA failed levels, but dramatically reduced This demonstrated that acts mainly through steric inhibition processing rather than cleavage target RNA, as ribozymes. Resistance anthracyclines Vinca alkaloids was clones. could not be correlated reduction tested MDR facilitators, gene 1 (mdr-1) resistance-associated (MRP), largely invariant, directly observed reductions resistance. profiles were, however, strikingly similar typical mdr-1 overexpressing lines. It cannot ruled out, therefore, Pglycoprotein activity, due post-translational modifications, may sole mechanism these targeted LRP, level cells, induce adriamycin. thesis provides first resistance, last line.