Nguyen Thi Mong Diep, Klett Danièle, Combarnous Yves
Physiologie de la Reproduction & des Comportements Laboratory, Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique & Environnementale (INRAe), University of Tours, Nouzilly 37380, France.
Faculty of Natural Sciences, Quy Nhon University, Quy Nhon 820000, Vietnam.
Korean J Physiol Pharmacol. 2021 May 1;25(3):189-195. doi: 10.4196/kjpp.2021.25.3.189.
Fluoxetine (FLX), a selective serotonin reuptake inhibitor antidepressant, exhibits various other mechanisms of action in numerous cell types and has been shown to induce cell death in cancer cells, paving the way for its potential use in cancer therapy. The aim of this study was to determine the off-target effects of the anti-depressant drug FLX, on the human ovarian granulosa tumor COV434 cells stimulated by forskolin (FSK), by measuring the real-time kinetics of intracellular cyclic AMP (cAMP), ATP level, cytoplasmic calcium ([Ca]) and survival of COV434 cells. We show that incubating COV434 cells with FLX (between 0.6 and 10 µM) induces a decrease in intracellular cAMP response to FSK, a drop in ATP content and stimulates cytoplasmic Ca accumulation in COV434 cells. Only the highest concentrations of FLX (5-10 µM) diminished cell viability. The present report is the first to identify an action mechanism of FLX in human tumor ovarian cells COV434 cells and thus opening the way to potential use of fluoxetine as a complementary tool, in granulosa tumor treatments.
氟西汀（FLX）是一种选择性5-羟色胺再摄取抑制剂类抗抑郁药，在多种细胞类型中展现出多种其他作用机制，并且已被证明可诱导癌细胞死亡，这为其在癌症治疗中的潜在应用铺平了道路。本研究的目的是通过测量细胞内环磷酸腺苷（cAMP）的实时动力学、ATP水平、细胞质钙（[Ca]）以及COV434细胞的存活率，来确定抗抑郁药FLX对由福斯高林（FSK）刺激的人卵巢颗粒细胞瘤COV434细胞的脱靶效应。我们发现，用FLX（0.6至10µM）孵育COV434细胞会导致细胞内对FSK的cAMP反应降低、ATP含量下降，并刺激COV434细胞内细胞质钙的积累。只有最高浓度的FLX（5至10µM）会降低细胞活力。本报告首次确定了FLX在人肿瘤卵巢细胞COV434细胞中的作用机制，从而为氟西汀作为颗粒细胞瘤治疗中的一种辅助工具的潜在应用开辟了道路。
