Treatment of resistant human colon cancer xenografts by a fluoxetine-doxorubicin combination enhances therapeutic responses comparable to an aggressive bevacizumab regimen

Mirit Argov, Rina Kashi, Dan Peer, Rimona Margalit

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Pre-clinical studies of multidrug resistance (MDR) usually address severe resistance, yet moderate MDR is already clinically-impeding. The purpose of this study was to characterize moderate drug resistance in human colon cancer, and it's modulation by fluoxetine. In vitro fluoxetine enhanced doxorubicin's cytotoxicity (10-fold), increased doxorubicin's intracellular accumulation (32%) and decreased efflux of intracellular doxorubicin (70%). In vivo, mild treatment with a doxorubicin-fluoxetine combination slowed-down tumor progression significantly (p < 0.001 vs. doxorubicin alone), comparable to aggressive treatment with bevacizumab. Collectively, our results suggest that combinations of fluoxetine with chemotherapeutic drugs (P-glycoprotein substrates) are worthy of further pursuit for moderate MDR in the clinic.

Original languageEnglish (US)
Pages (from-to)118-125
Number of pages8
JournalCancer Letters
Volume274
Issue number1
DOIs
StatePublished - Feb 8 2009

Keywords

  • Bevacizumab
  • Colon cancer
  • Doxorubicin
  • Fluoxetine
  • Multidrug resistance
  • P-glycoprotein

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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