PT  - JOURNAL ARTICLE
AU  - WEI-TING CHEN
AU  - YUAN-HSIN TSAI
AU  - PEGGY TAN
AU  - FEI-TING HSU
AU  - HUI-MIN DAVID WANG
AU  - WEI-CHIN LIN
AU  - FENG-HUEI LIN
AU  - CHING-TE WU
TI  - Fluoxetine Inhibits STAT3-mediated Survival and Invasion of Osteosarcoma Cells
AID  - 10.21873/anticanres.16265
DP  - 2023 Mar 01
TA  - Anticancer Research
PG  - 1193--1199
VI  - 43
IP  - 3
4099  - http://ar.iiarjournals.org/content/43/3/1193.short
4100  - http://ar.iiarjournals.org/content/43/3/1193.full
SO  - Anticancer Res2023 Mar 01; 43
AB  - 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.