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


CONCLUSIONS
WIN can inhibit the EMT of GC cells through the downregulation of COX-2.
Department of Gastroenterology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
Xiangshu
X
Xian
Liuye
L
Huang
Bo
B
Zhang
Chengrong
C
Wu
Jun
J
Cui
Zhihua
Z
Wang
D048588:Benzoxazines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D048588:Benzoxazines; D051546:Cyclooxygenase 2; D009025:Morpholines; D009281:Naphthalenes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone