Fluoxetine Enhances Anti-tumor Activity of Paclitaxel in Gastric Adenocarcinoma Cells by Triggering Apoptosis and Necroptosis
Autor: | Wah Wah Po, Uy Dong Sohn, Tin Myo Khing |
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Rok vydání: | 2019 |
Předmět: |
Cancer Research
Programmed cell death Paclitaxel Necroptosis Apoptosis Adenocarcinoma 03 medical and health sciences chemistry.chemical_compound Necrosis 0302 clinical medicine Stomach Neoplasms Fluoxetine Tumor Cells Cultured Cytotoxic T cell Humans DAPI Viability assay Propidium iodide Cell Proliferation Cell Cycle Drug Synergism General Medicine Antineoplastic Agents Phytogenic Oncology chemistry Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research Selective Serotonin Reuptake Inhibitors |
Zdroj: | Anticancer research. 39(11) |
ISSN: | 1791-7530 |
Popis: | BACKGROUND/AIM Fluoxetine, an antidepressant, has cytotoxic effects on several cancer cell lines, while paclitaxel is an antineoplastic agent for various cancers. The aim of this study was to evaluate whether fluoxetine enhances the cytotoxic effect of paclitaxel in gastric adenocarcinoma cells and determine the mechanism of cell death. MATERIALS AND METHODS 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to examine cell viability and perform cell cycle analysis. Annexin V propidium iodide (PI) staining, 4',6-diamidino-2-phenylindole (DAPI) staining, caspase-3/7 assay, and western blot analysis were performed for determining cell death. RESULTS Fluoxetine enhanced the anti-proliferative effect of paclitaxel. Fluoxetine-paclitaxel combination caused G2/M arrest and increased events in the sub G0/G1 phase in a time and dose-dependent manner, indicating apoptotic cell death. Combination treatment caused an increase in early apoptotic and late apoptotic cell death compared to single treatment alone. CONCLUSION Fluoxetine enhanced the antiproliferation effect of paclitaxel in gastric adenocarcinoma AGS cells and the combination caused cell death by triggering apoptosis and necroptosis. |
Databáze: | OpenAIRE |
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