WIN 55,212-2 Inhibits the Epithelial Mesenchymal Transition of Gastric Cancer Cells via COX-2 Signals

Cell Physiol Biochem. 2016;39(6):2149-2157. doi: 10.1159/000447910. Epub 2016 Nov 2.

Abstract

Background: Cannabinoids (the active components of Cannabis sativa) and their derivatives have received considerable interest due to reports that they can affect the tumor growth, migration, and metastasis. Previous studies showed that the cannabinoid agonist WIN 55,212-2 (WIN) was associated with gastric cancer (GC) metastasis, but the mechanisms were unknown.

Methods: The effects of WIN on GC cell migration and invasion were analyzed by the wound-healing assay and Transwell assay. Quantitative real-time PCR and Western blot were used to evaluate changes in expression of COX-2 and EMT associated markers in SGC7901 and AGS cells.

Results: WIN inhibited cell migration, invasion, and epithelial to mesenchymal transition (EMT) in GC. WIN treatment resulted in the downregulation of cyclooxygenase-2 (COX-2) expression and decreased the phosphorylation of AKT, and inhibited EMT in SGC7901 cells. Decreased expression of COX-2 and vimentin, and increased expression of E-cadherin, which was induced by WIN, were normalized by overexpression of AKT, suggesting that AKT mediated, at least partially, the WIN suppressed EMT of GC cells.

Conclusion: WIN can inhibit the EMT of GC cells through the downregulation of COX-2.

MeSH terms

  • Benzoxazines / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Down-Regulation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Morpholines / pharmacology*
  • Naphthalenes / pharmacology*
  • Neoplasm Invasiveness
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • Benzoxazines
  • Morpholines
  • Naphthalenes
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Cyclooxygenase 2
  • Proto-Oncogene Proteins c-akt