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Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Fluoxetine Suppresses Osteosarcoma Progression In Vivo by Inducing Apoptosis and Inhibiting the AKT/mTOR/NF-κB
Yu-Hsi Chen1, Chi-Huan Li2, Shih-Wei Liu3,4
1Department of Orthopedics, Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.
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-[Formula: see text]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.
Insights
Fluoxetine effectively reduced osteosarcoma (OSCC) tumor growth and metastasis in vivo. This antidepressant shows potential as a novel therapeutic agent for OSCC by inducing apoptosis and inhibiting key signaling pathways.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Osteosarcoma (OSCC) presents a significant challenge, driving the need for new treatments.
- Novel therapeutic strategies are crucial for improving outcomes in OSCC patients.
Purpose of the Study:
- To investigate the anti-tumor effects of fluoxetine in an in vivo OSCC model.
- To evaluate fluoxetine's impact on tumor growth, metastasis, and molecular mechanisms in OSCC.
Main Methods:
- Mice bearing U-2 OS cell xenografts were treated with varying doses of fluoxetine (10 or 20 mg/kg).
- Tumor growth, metastasis, and systemic toxicity were assessed via histopathological and biochemical analyses.
- Molecular mechanisms, including apoptosis, angiogenesis, epithelial-mesenchymal transition, and key signaling pathways, were investigated.
Main Results:
- Fluoxetine treatment led to a dose-dependent decrease in tumor volume and weight without significant toxicity.
- Apoptosis was induced via activation of the caspase cascade (caspase-8, -9, -3).
- Metastasis was inhibited by suppressing VEGF and MMP-9, reducing epithelial-mesenchymal transition, and disrupting AKT/mTOR and NF-κB signaling.
Conclusions:
- Fluoxetine exhibits significant anti-tumor activity against OSCC in vivo.
- The drug induces apoptosis, inhibits metastasis, and targets critical oncogenic signaling pathways.
- Fluoxetine holds promise as a potential therapeutic agent for osteosarcoma, meriting further clinical investigation.
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