PT  - JOURNAL ARTICLE
AU  - CHEN, YU-HSI
AU  - LI, CHI-HUAN
AU  - LIU, SHIH-WEI
AU  - HSU, FEI-TING
AU  - KU, MING-CHOU
TI  - Fluoxetine Suppresses Osteosarcoma Progression <em>In Vivo</em> by Inducing Apoptosis and Inhibiting the AKT/mTOR/NF-κB Signaling Pathway
AID  - 10.21873/anticanres.17530
DP  - 2025 Apr 01
TA  - Anticancer Research
PG  - 1465--1480
VI  - 45
IP  - 4
4099  - http://ar.iiarjournals.org/content/45/4/1465.short
4100  - http://ar.iiarjournals.org/content/45/4/1465.full
SO  - Anticancer Res2025 Apr 01; 45
AB  - Background/Aim: Osteosarcoma (OSCC) remains a significant health concern, necessitating novel therapeutic strategies. This study investigated the anti-tumor effects of fluoxetine in an in vivo OSCC model.Materials and Methods: Mice inoculated with U-2 OS cells were treated with fluoxetine (10 or 20 mg/kg) to evaluate tumor growth, metastasis, and underlying molecular mechanisms.Results: Fluoxetine treatment resulted in a dose-dependent reduction in tumor volume and weight, without causing systemic toxicity, as confirmed by histopathological and biochemical analyses. Mechanistically, fluoxetine activated caspase-dependent apoptosis by up-regulating cleaved caspase-8, caspase-9, and caspase-3. It also inhibited OSCC metastasis by suppressing VEGF and MMP-9 expression, reducing epithelial-mesenchymal transition markers. Furthermore, fluoxetine significantly reduced the phosphorylation of AKT, PRAS40, mTOR, and NF-B, thereby disrupting key tumorigenic signaling pathways.Conclusion: Fluoxetine demonstrates promising anti-tumor activity in OSCC by inducing apoptosis, inhibiting metastasis, and targeting oncogenic signaling pathways. These findings suggest that fluoxetine may serve as a potential therapeutic agent for OSCC, warranting further investigation for clinical application.