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

Anticancer Res. 2018 Sep;38(9):5201-5210. doi: 10.21873/anticanres.12843.

Abstract

Background/aim: The aim of present study was to verify the effect of fluoxetine on DNA repair and metastatic potential in non-small cell lung cancer (NSCLC) in vitro.

Materials and methods: Highly metastatic NSCLC CL1-5-F4 cells were used in this study. Cells were treated with different concentrations of fluoxetine or QNZ (NF-ĸB inhibitor) for 48 h. After treatment, cell viability, apoptotic signaling, NF-ĸB activation, expression of DNA repair and metastasis-associated proteins, and cell migration/invasion were evaluated by (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay, flow cytometry, NF-ĸB reporter gene, western blotting, and cell migration/invasion assay, respectively.

Results: Fluoxetine induced apoptosis and reduced cell viability, NF-ĸB activation, expression of DNA repair and metastasis-associated proteins, and cell migration/invasion in CL1-5-F4 cells. Also, NF-ĸB activation was the critical factor in fluoxetine-inhibited metastatic potential.

Conclusion: Fluoxetine induced apoptosis and inhibited DNA repair and metastatic potential in NSCLC CL1-5-F4 cells.

Keywords: DNA repair; NF-ĸB; Non-small cell lung cancer; fluoxetine; metastatic potential.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • DNA Repair / drug effects*
  • Fluoxetine / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • NF-kappa B / genetics*
  • Neoplasm Metastasis
  • Phenyl Ethers / pharmacology
  • Quinazolines / pharmacology
  • Signal Transduction / drug effects

Substances

  • EVP 4593
  • NF-kappa B
  • Phenyl Ethers
  • Quinazolines
  • Fluoxetine