Fluoxetine Inhibits DNA Repair and NF-ĸB-modulated Metastatic Potential in Non-small Cell Lung Cancer

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality.
• Understanding the molecular mechanisms underlying NSCLC metastasis and DNA repair is crucial for developing effective therapies.
• Investigating novel therapeutic agents targeting these pathways is of significant clinical interest.

Purpose of the Study:

• To investigate the in vitro effects of fluoxetine on DNA repair mechanisms in NSCLC.
• To evaluate the impact of fluoxetine on the metastatic potential of NSCLC cells.
• To elucidate the role of NF-κB signaling in fluoxetine's anti-cancer effects.

Main Methods:

• Utilized highly metastatic NSCLC CL1-5-F4 cell line.
• Treated cells with varying concentrations of fluoxetine or QNZ (NF-κB inhibitor).
• Assessed cell viability, apoptosis, NF-κB activation, DNA repair protein expression, and cell migration/invasion using multiple assays.

Main Results:

• Fluoxetine significantly reduced cell viability and induced apoptosis in NSCLC cells.
• Fluoxetine treatment decreased NF-κB activation, DNA repair protein expression, and cell migration/invasion.
• Inhibition of NF-κB activation was identified as a critical mediator of fluoxetine's anti-metastatic effects.

Conclusions:

• Fluoxetine demonstrates potent anti-cancer properties against NSCLC in vitro.
• Fluoxetine effectively inhibits DNA repair and metastatic potential in NSCLC cells.
• Targeting NF-κB signaling represents a promising therapeutic strategy for NSCLC treatment with fluoxetine.