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

被引：43

作者：

Argov, Mirit ^{[1
]}

Kashi, Rina ^{[2
]}

Peer, Dan ^{[1
]}

Margalit, Rimona ^{[1
]}

机构：

[1] Tel Aviv Univ, Dept Biochem, IL-69978 Tel Aviv, Israel

[2] Teva Pharmaceut Ind, Teva Innovat Ventures, Netanya, Israel

来源：

CANCER LETTERS | 2009年 / 274卷 / 01期

关键词：

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

D O I：

10.1016/j.canlet.2008.09.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

引用

页码：118 / 123

页数：6

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