COX-2Regulated Snail Expression And Involved In Invasion And Migration Of Gastric Cancer Via Notch1Signaling Pathway

ObjectiveTo aim Notchl, Notch2, Notch3, Jaggedl and COX-2expression in gastric cancer and the relationship between those factors and clinicopathological parameters, we further explored that COX-2regulated Snail expression which involved in the invasion and metastasis of gastric tumor through Notchl signaling pathway. The COX-2/Notchl/Snail signaling pathways that involved in invasion and metastasis of gastric cancer may provide new targets and theoretical basis for future targeted and pathogenesis of gastric cancer.MethodsWe used qPCR and Western Blotting to detect the different expression ofNotchl, Notch2, Notch3, Jagged1and COX-2between gastric cancer tissues and adjacent non-tumor mucosa, further analysed the relationship between Notch signaling and clinicopathological parameters of gastric cancer. We detected the Notchl and COX-2expression in human gastric mucosa cell line GES-1and gastric cancer cell lines with different differentiation, and then we selected SGC-7901and BGC-823cells for next experiments. SGC-7901and BGC-823cells were treated with Celecoxib and Prostaglandin E2(PGE2) in vitro to detect the effect on Notchl expression. Finally, we used siRNA/COX-2and/or siRNA/Notchl to knockdown COX-2and/or Notchl expression in SGC-7901and BGC-823, as well as to detect the change of Snail mRNA and protein. The relationship of COX-2and Notchl was clarified, and to explore the effect on Snail expression and migration ability of gastri cancer cells.Results1. The expression ofNotchl intracellular domain(N1IC) of gastric cancer tissues were significantly reduced which compared with adjacent non-tumor tissues, which related with the invasion depth and TNM stage.2. The mRNA level of Notch2and Notch3were significantly increased in gastric cancer tissues. Increased N21C related with distant metastasis of gastric cancer and increased Notch3involved in onset age.The mRNA level of Jaggedl also significantly increased in gastric cancer tissues and associated with distant metastasis of gastric cancer.3. High expression of COX-2in gastric cancer tissues were concerned with differentiation and invasion depth.4. COX-2and Notchl in different cell lines showed a reverse expression model.5. Inhibition of COX-2could up-regulated espression and activation of Notchl in gastric cancer cells, conversely, down-regulated its expression and activation.Conclusions1. Notch signaling family may have different role in gastric cancer, and it may be a reverse relationship between COX-2and Notch1in gastric cancer.2. Higher cox-2expression in gastric cancer cells could reduce Notchl and increase Snail levels, but it is unclear that Notchl could regulate expression of COX-2in gastric cancer cells. Snail expression regulaed by Notchl in gastric cancer cells may be different due to cell context.