Dual inhibition of 5-LOX and COX-2 suppresses esophageal squamous cell carcinoma

Cancer Lett. 2011 Oct 1;309(1):19-26. doi: 10.1016/j.canlet.2011.05.010. Epub 2011 Jun 8.

Abstract

COX-2 and 5-LOX are up-regulated in ESCC. This study aims to determine the efficacy of COX-2 inhibitor, 5-LOX inhibitor and their combination on ESCC. Nimesulide can suppress cell growth and promote apoptosis, accompanied with a decrease of PGE(2) production. AA861 has the similar effect with a down-regulation of LTB(4). In animal experiment, the tumor volumes in drug-treated groups were significantly smaller with the lowest rates of Ki-67 positive cells. In conclusion, either COX-2 inhibitor or 5-LOX inhibitor can suppress ESCC. Dual inhibition of COX-2 and 5-LOX pathway may present a superior anticancer efficacy to either inhibition of COX-2 or 5-LOX alone.

MeSH terms

  • Animals
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / enzymology
  • Carcinoma, Squamous Cell* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Down-Regulation / drug effects
  • Drug Synergism
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / enzymology
  • Esophageal Neoplasms* / pathology
  • Humans
  • Lipoxygenase Inhibitors / pharmacology*
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation

Substances

  • Cyclooxygenase 2 Inhibitors
  • Lipoxygenase Inhibitors
  • Arachidonate 5-Lipoxygenase
  • Cyclooxygenase 2
  • PTGS2 protein, human