S9788 modulation of P-glycoprotein- and multidrug-related protein-mediated multidrug resistance by Servier 9788 in doxorubicin resistant MCF7 cells

Inherent or acquired resistance to multiple natural drugs, termed multidrug resistance (MDR), represents a major obstacle to chemotherapy. Expression of P-glycoprotein (P-gp) in MCF7mdr and MCF7R resistant cells was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. MCF7R, but not the MDR1 gene-transfected MCF:mdr cells, expressed multidrug-related protein (MRP) concomitantly. Efficacy of an MDR modulator, designated as Servier 9788 (S9788), was estimated by doxorubicin (Dox) sensitization, Dox incorporation, and functional rhodamine 123 assay on MCF7 cell lines. Results showed that S9788 modulates the P-gp-associated MDR of MCF7mdr cells as well as the Multidrug-related protein-associated MDR of MCF7R cells. BIOCHEM PHARMACOL 56;4:497-502, 1998. (C) 1998 Elsevier Science Inc.