STAT3 Inactivation and Induction of Apoptosis Associate With Fluoxetine-inhibited Epithelial-mesenchymal Transition and Growth of Triple-negative Breast Cancer In Vivo

Abstract

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.

Materials and methods: We established an 4T1 bearing animal model, an orthotopic TNBC model, to identify the mechanism and therapeutic efficacy of fluoxetine.

Results: 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.

Conclusion: Fluoxetine may induce an anti-TNBC effect via inactivating STAT3 signaling transduction and triggering the caspase-mediated apoptotic pathway.

Keywords: Fluoxetine; STAT3; apoptosis; epithelial-to-mesenchymal transition; triple-negative breast cancer.