Cyclooxygenase-2 inhibitor, celecoxib, inhibits leiomyoma cell proliferation through the nuclear factor κB pathway

Reprod Sci. 2014 Sep;21(9):1187-95. doi: 10.1177/1933719114542010. Epub 2014 Jul 6.

Abstract

Our aim was to investigate whether celecoxib, a cyclooxygenase 2 (COX-2) inhibitor, decreases the in vitro proliferation of leiomyoma cells if the inflammatory pathway is blocked. Menstruation is an inflammation of uterus that produces cytokines and prostanoids, but the inflammatory mechanism underlying the growth of leiomyoma remains unexplained. Using in vitro cultures of leiomyoma cells obtained from 5 patients who underwent hysterectomy, cell proliferation, inflammatory signaling, transcription factors, growth factors, and extracellular matrix were examined by (4,5-dimethylthiaxol-2-yi)-2,5-diphenyltetraxolium bromide assay, immunoblotting, and quantitative polymerase chain reaction. Prostaglandin E2 was used to induce menstruation-like condition in the cells. We found that celecoxib inhibited COX-2 through the expression of nuclear factor κB in the cells. Celcoxib also decreased the gene expression of interleukin 6, tumor necrosis factor α, collagen A, fibronectin, platelet-derived growth factor, epidermal growth factor, and transforming growth factor β. In conclusion, the present study indicated that celecoxib could inhibit leiomyoma cell proliferation through blocking the inflammatory pathway that is probably one of the mechanisms underlying its pathogenesis.

Keywords: NF-kappa B; celecoxib; cyclooxygenase 2 inhibitors; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Celecoxib
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology*
  • Cyclooxygenase 2 / biosynthesis
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Female
  • Humans
  • Leiomyoma / drug therapy
  • Leiomyoma / metabolism*
  • Leiomyoma / pathology
  • Middle Aged
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Pyrazoles / pharmacology*
  • Pyrazoles / therapeutic use
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Sulfonamides / pharmacology*
  • Sulfonamides / therapeutic use
  • Tumor Cells, Cultured
  • Uterine Neoplasms / drug therapy
  • Uterine Neoplasms / metabolism*
  • Uterine Neoplasms / pathology

Substances

  • Cyclooxygenase 2 Inhibitors
  • NF-kappa B
  • Pyrazoles
  • Sulfonamides
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Celecoxib