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.

Anticancer Research
|March 28, 2025
PubMed
Abstract

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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