Abstract
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.
- Received February 6, 2025.
- Revision received February 18, 2025.
- Accepted February 20, 2025.
- Copyright © 2025 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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