Xian Xiangshu, Huang Liuye, Zhang Bo, Wu Chengrong, Cui Jun, Wang Zhihua
Department of Gastroenterology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
Cell Physiol Biochem. 2016;39(6):2149-2157. doi: 10.1159/000447910. Epub 2016 Nov 2.
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.
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.
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.
WIN can inhibit the EMT of GC cells through the downregulation of COX-2.
大麻素（大麻的活性成分）及其衍生物因有报道称它们可影响肿瘤生长、迁移和转移而受到广泛关注。先前的研究表明，大麻素激动剂WIN 55,212-2（WIN）与胃癌（GC）转移有关，但其机制尚不清楚。
采用划痕实验和Transwell实验分析WIN对GC细胞迁移和侵袭的影响。运用定量实时PCR和蛋白质免疫印迹法评估SGC7901和AGS细胞中COX-2及上皮-间质转化（EMT）相关标志物表达的变化。
WIN抑制GC细胞的迁移、侵袭及上皮-间质转化（EMT）。WIN处理导致环氧化酶-2（COX-2）表达下调，AKT磷酸化水平降低，并抑制SGC7901细胞的EMT。WIN诱导的COX-2和波形蛋白表达降低以及E-钙黏蛋白表达增加，通过AKT过表达得以恢复正常，这表明AKT至少部分介导了WIN对GC细胞EMT的抑制作用。
WIN可通过下调COX-2抑制GC细胞的EMT。
