The Expression Of The Key Factor Of Notch Pathway And Effects Of Notch Receptor-blocker On Gastric Cancer Cells

Notch signaling plays an important role in maintaining progenitor/stem cell population as well as a balance between cell proliferation, differentiation and apoptosis. Aberrantly activated Notch signaling has been observed during the carcinogenesis of many human cancers, such as lung cancer, renal cancer, ovarian cancer and colon cancer. Notch receptor as the promoter or suppressor could be based on cell types and different micro-environment respectively, and different receptor have distinct activities and outcomes. At present, the roles of Notch pathway in gastric cancer were not clear.In this study, the expression of Notch signaling receptors, ligand and target gene in the development of gastric cancer were analysized by immunohistochemistry, RT-PCR, Western Blot and other methods. And to determine the role of Notch pathway in gastric cancer, we observed the biological behavior of gastric cancer cells with Notch inhibitor- GSI. In addition, we studied the relationship of Notch pathway and H. Pylori- the most important risk factor for gastric cancer.The results showed that the expression of receptor Notch 2 and ligand Jagged 1 was significantly higher in cancer tissues than the normal tissues. It was confirmed the mRNA and protein levels of Notch 2 and Jagged 1, Dll 4 increased in gastric cancer cell lines. However, the expression of Notch 1 was no significant difference between tumor cell lines and normal cell. It was suggesting that Notch 1 receptor may not be involved in the process of gastric cancer. Gastric cancer cell could be induced to apoptosis withγ-enzyme, and cell proliferation was inhibited at the same time. It is intresting that there is no significantly difference of PI3K/AKT pathway between them. Meanwhile we found Dll 4 expression levels increased after the cell treated with GSI. It was suggested that Notch ligand-independent pathway exists in gastric cancer and it has opposing effects with Notch receptor pathway. In other hand, cell proliferation was inhibited with H. pylori infection. It showed that all of Notch receptor, ligand and target gene expression increased by RT-PCR.In conclusion, this study found that Notch signaling pathway has abnormal activation in gastric cancer. Notch 1 may not be involved in tumor promotion process. Inhibiting Notch receptor can induce apoptosis and inhibit cancer cell proliferation, and it may activate the Notch ligand-independent way. In addition, H. pylori infection can activate the Notch signaling pathway, which may be one of the carcinogenic mechanisms. Thus, Notch receptor inhibitor could be a potential targeted medicine.