Regular Article

British Journal of Cancer (2001) 85, 1987–1997. doi:10.1054/bjoc.2001.2165 www.bjcancer.com
Published online 11 December 2001

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

E V Batrakova1, S Li1, W F Elmquist1, D W Miller1, V Y Alakhov2 and A V Kabanov1

  1. 1College of Pharmacy, Department of Pharmaceutical Sciences, Nebraska Medical Center, 986025, Omaha, NE, 68198-6025, USA
  2. 2Supratek Pharma Inc., 513 blvd. des Prairies, Case Postale 100, Laval, PQ, H7N 4Z3, Canada

Received 14 December 2000; Revised 25 September 2001; Accepted 27 September 2001.

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Abstract

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. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords:

ATP, doxorubicin, MDR, Pluronic, sensitisation

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