1: Cancer Lett. 2009 Feb 8;274(1):118-25. Epub 2008 Oct 11.
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Treatment of resistant human colon cancer xenografts by a fluoxetine-doxorubicin combination enhances therapeutic responses comparable to an aggressive bevacizumab regimen.
Argov M,
Kashi R,
Peer D,
Margalit R.
Department of Biochemistry, Tel Aviv University, Tel Aviv 69978, Israel.
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.
PMID: 18851896 [PubMed - indexed for MEDLINE