Fluoxetine Inhibits STAT3-mediated Survival and Invasion of Osteosarcoma Cells

Background/Aim: Osteosarcoma (OS) is a common primary malignancy of bone in adolescents. Its highly metastatic characteristics can lead to treatment failure and poor prognosis. Although standard treatments, including surgery, radiotherapy, and chemotherapy, have progressed in the past decade, treatment options to overcome metastatic progression remain sparse. Fluoxetine, an anti-depressant, has been widely used in patients with cancer for their mental issues and was reported to possess antitumor potential. However, the effect of fluoxetine on OS remains unclear. Materials and Methods: In this study, we used cell viability, invasion/migration transwell, wound-healing and aortic ring assays to identify the effects of fluoxetine on metastasis and progression in OS. Results: Fluoxetine induced cytotoxicity in OS cells by activating both extrinsic/intrinsic apoptosis signaling pathways. Proliferation and anti-apoptosis-related factors such as cyclin D1 and X-linked inhibitor of apoptosis were suppressed by fluoxetine. Additionally, fluoxetine suppressed the invasive/migratory abilities of OS and inhibited the development of angiogenesis by reducing the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Metastasis-associated factors, vascular endothelial growth factors, matrix metallopeptidase 2 and-9, were all reduced in OS cells by fluoxetine treatment. Conclusion: Fluoxetine not only induces cytotoxicity and apoptosis of OS cells, but also suppresses metastasis and angiogenesis by targeting STAT3.

Automated summary

Osteosarcoma is a common bone malignancy with high metastatic characteristics and poor prognosis. Fluoxetine, an anti-depressant, has been shown to have antitumor potential. In this study, fluoxetine was found to induce cytotoxicity and apoptosis in osteosarcoma cells, while also suppressing metastasis and angiogenesis by targeting STAT3.