Department of Radiology, Cathay General Hospital, Taipei, Taiwan, R.O.C.
School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, R.O.C.
Anticancer Res. 2022 Aug;42(8):3807-3814. doi: 10.21873/anticanres.15871.
BACKGROUND/AIM: Breast cancer (BC) is the most common cancer and second leading cause of death in women worldwide. Triple-negative breast cancer (TNBC) is the most aggressive type of BC, while the treatment option is limited and has long been considered as a major unmet need. Meta-analysis indicated the anti-tumor potential of anti-depressants, especially selective serotonin-reuptake inhibitors (SSRIs). The SSRI fluoxetine has been shown to suppress BC and ovarian cancer cell growth; however, whether it suppresses tumor progression in vivo is unclear.
We established an 4T1 bearing animal model, an orthotopic TNBC model, to identify the mechanism and therapeutic efficacy of fluoxetine.
Tumor growth evaluated by caliper and computed tomography scan demonstrated the inhibition effect by fluoxetine treatment. Immunohistochemistry showed that the expression of STAT3-mediated epithelial-to-mesenchymal transition (EMT) proteins and apoptosis-related proteins was decreased.
Fluoxetine may induce an anti-TNBC effect via inactivating STAT3 signaling transduction and triggering the caspase-mediated apoptotic pathway.
背景/目的：乳腺癌（BC）是全球最常见的癌症和女性死亡的第二大主要原因。三阴性乳腺癌（TNBC）是最具侵袭性的 BC 类型，而治疗选择有限，长期以来一直被认为是一个主要的未满足需求。荟萃分析表明抗抑郁药，特别是选择性 5-羟色胺再摄取抑制剂（SSRIs）具有抗肿瘤潜力。SSRIs 氟西汀已被证明可抑制 BC 和卵巢癌细胞生长；然而，其在体内是否抑制肿瘤进展尚不清楚。
我们建立了一个携带 4T1 的动物模型，即原位 TNBC 模型，以确定氟西汀的作用机制和治疗效果。
卡尺和计算机断层扫描评估的肿瘤生长表明氟西汀治疗具有抑制作用。免疫组织化学显示，STAT3 介导的上皮-间充质转化（EMT）蛋白和凋亡相关蛋白的表达减少。
氟西汀可能通过抑制 STAT3 信号转导和触发半胱天冬酶介导的凋亡途径来诱导抗 TNBC 作用。
