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

Biochem Pharmacol. 1998 Aug 15;56(4):497-502. doi: 10.1016/s0006-2952(98)00007-0.

Abstract

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 MCF7mdr 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology*
  • ATP-Binding Cassette Transporters / physiology*
  • Antibiotics, Antineoplastic / pharmacology*
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / pharmacology*
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Humans
  • Multidrug Resistance-Associated Proteins
  • Piperidines / pharmacology*
  • Rhodamine 123
  • Rhodamines / metabolism
  • Triazines / pharmacology*
  • Tumor Cells, Cultured

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Antibiotics, Antineoplastic
  • Multidrug Resistance-Associated Proteins
  • Piperidines
  • Rhodamines
  • Triazines
  • S 9788
  • Rhodamine 123
  • Doxorubicin