Mechanism of sensitization of MDR cancer cells by Pluronic block copolymers: Selective energy depletion

Br J Cancer. 2001 Dec 14;85(12):1987-97. doi: 10.1054/bjoc.2001.2165.


This paper, for the first time, demonstrates that exposure of cells to the poly(ethylene oxide)-poly(propylene oxide) block copolymer, Pluronic P85, results in a substantial decrease in ATP levels selectively in MDR cells. Cells expressing high levels of functional P-glycoprotein (MCF-7/ADR, KBv; LLC-MDR1; Caco-2, bovine brain microvessel endothelial cells [BBMECs]) are highly responsive to Pluronic treatment, while cells with low levels of P-glycoprotein expression (MCF-7, KB, LLC-PK1, human umbilical vein endothelial cells [HUVECs] C2C12 myoblasts) are much less responsive to such treatment. Cytotoxicity studies suggest that Pluronic acts as a chemosensitizer and potentiates cytotoxic effects of doxorubicin in MDR cells. The ability of Pluronic to inhibit P-glycoprotein and sensitize MDR cells appears to be a result of ATP depletion. Because many mechanisms of drug resistance are energy dependent, a successful strategy for treating MDR cancer could be based on selective energy depletion in MDR cells. Therefore, the finding of the energy-depleting effects of Pluronic P85, in combination with its sensitization effects is of considerable theoretical and practical significance.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / deficiency
  • Adenosine Triphosphate / metabolism
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Antibiotics, Antineoplastic / therapeutic use
  • Biological Transport, Active / drug effects
  • Brain / blood supply
  • Capillaries / cytology
  • Cattle
  • Cell Line / drug effects
  • Cell Line / metabolism
  • Doxorubicin / pharmacology
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Endothelium, Vascular / cytology
  • Energy Metabolism / drug effects*
  • Humans
  • KB Cells / drug effects
  • KB Cells / metabolism
  • Kinetics
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / metabolism
  • Neoplasms / pathology
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Poloxalene / pharmacology*
  • Swine
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Umbilical Veins / cytology


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibiotics, Antineoplastic
  • Neoplasm Proteins
  • pluronic block copolymer p85
  • Doxorubicin
  • Adenosine Triphosphate
  • Poloxalene
  • Adenosine Triphosphatases