Potentiation of the reversal activity of SDZ PSC833 on multi-drug resistance by an anti-P-glycoprotein monoclonal antibody MRK-16

Int J Cancer. 1996 Jul 29;67(3):435-40. doi: 10.1002/(SICI)1097-0215(19960729)67:3<435::AID-IJC20>3.0.CO;2-5.


SDZ PSC833 (PSC833), an analogue of cyclosporines, is one of the most potent modulators of multi-drug resistance (MDR). We previously reported that MRK-16, an anti-P-glycoprotein MAb, enhanced MDR reversal activity of cyclosporin A (CsA) through inhibition of P-glycoprotein-mediated CsA transport. We have examined here whether MRK-16 can enhance MDR reversal activity of PSC833. We found that MRK-16 potentiated the MDR reversal activity of PSC833, and of CsA, in MDR sublines of human myelocytic leukemia K562 and human ovarian cancer A2780 cells. Like MRK-16 combined with CsA, MRK-16 enhanced the effect of a sub-optimum dose of PSC833 on vincristine accumulation in MDR cells. However, MRK-16 could not increase cellular accumulation of PSC833 in MDR tumor cells, yet it could increase cellular accumulation of CsA. P-glycoprotein could not transport PSC833 but could transport CsA. Our results indicate that MRK-16 potentiates the MDR reversal activity of both PSC833 and CsA, yet also suggest that the molecular mechanism of the potentiation differs between the two substances.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / immunology*
  • Affinity Labels
  • Antibodies, Monoclonal / pharmacology*
  • Cyclosporine / pharmacology
  • Cyclosporins / pharmacokinetics
  • Cyclosporins / pharmacology*
  • Drug Resistance, Multiple*
  • Drug Synergism
  • Humans
  • Leukemia, Myeloid / drug therapy
  • Leukemia, Myeloid / metabolism
  • Tumor Cells, Cultured
  • Vincristine / pharmacokinetics
  • Vincristine / pharmacology


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Affinity Labels
  • Antibodies, Monoclonal
  • Cyclosporins
  • Vincristine
  • Cyclosporine
  • valspodar