title: Fluoxetine synergys with anticancer drugs to overcome multidrug resistance in breast cancer cells.
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.
authors.affiliation: Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.forename: Jingjing
authors.initials: J
authors.lastname: Duan
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Ganping
authors.initials: G
authors.lastname: Zhou
authors.forename: Rongkan
authors.initials: R
authors.lastname: Wang
authors.forename: Liwu
authors.initials: L
authors.lastname: Fu
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004357:Drug Synergism; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D005473:Fluoxetine; D019253:Proto-Oncogene Proteins c-bcl-2; D017367:Selective Serotonin Reuptake Inhibitors; D016159:Tumor Suppressor Protein p53