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 language | English |
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Pages (from-to) | 118-125 |
Number of pages | 8 |
Journal | Cancer Letters |
Volume | 274 |
Issue number | 1 |
DOIs | |
State | Published - 8 Feb 2009 |
Keywords
- Bevacizumab
- Colon cancer
- Doxorubicin
- Fluoxetine
- Multidrug resistance
- P-glycoprotein