Fluoxetine synergys with anticancer drugs to overcome multidrug resistance in breast cancer cells.

Tumour Biol. 2012 Oct;33(5):1299-306.

Zhou T, Duan J, Wang Y, Chen X, Zhou G, Wang R, Fu L, Xu F.

Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.

Abstract

Multidrug resistance (MDR) is the main obstacle in breast cancer chemotherapy, a reversal reagent with high reversal effect but low toxicity is the hotpot issue at present. The antidepressant fluoxetine (FLX) is a new highly effective chemosensitizer; however, the possible mechanism of FLX in reversal of MDR is unclear. In this study, the effect of FLX on MDR mediated by apoptosis was researched in resistant/sensitive breast cancer cells, which treated by FLX/adriamycin (ADM)/paclitaxel (PTX) alone or FLX-ADM, FLX-PTX combination. Apoptosis assay demonstrated that FLX combined with ADM enhanced the proportion of apoptosis remarkably in MCF-7/ADM but not MCF-7 cells; however, increased the apoptosis rates in both cells when FLX-PTX combination. Results of apoptosis proteins assay showed a upgrade of p53 and a downgrade of Bcl-2 level by FLX-ADM or FLX-PTX combinations in both cells. Our findings indicated that by synergism with anticancer drugs, FLX modulation of apoptosis via targeting p53 and Bcl-2 expression, FLX reverse the breast cancer cell’s resistance and enhance the chemosensitivity to ADM and PTX.

PMID: 22549660

 

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