The Study Of CaMKⅡ γ Promoting The Proliferation Of Gastric Cancer Cells In Vivo And In Vitro And Its Possible Mechanism

Background Gastric cancer is one of the most common malignant tumors in digestive tract.Multiple signaling pathways participate in gastric carcinogenesis and gastric cancer progression.However,the exact molecular mechanisms involved in gastric cancer remain unclear.Ca/calmodulin-dependent protein kinase Ⅱγ(CaMKⅡγ)plays a significant role in cell proliferation and differentiation.It is also regarded as a critical regulator in cancer-related signaling pathways.Previous studies have shown that CaMKⅡγ is highly expressed in liver cancer and colorectal cancer.Considering that gastric cancer and colorectal cancer is originated from the same stem cells,we wonder whether CaMKⅡγ is associated with gastric cancer or not.Aims To evaluate the expression profile of CaMKⅡγ in gastric cancer and explore its role in gastric cancer and its possible mechanism,with a view to provide a potential target for therapy of gastric cancer.Methods CaMKⅡγ expression in 16 gastric cancer tumor tissues was examined by qRT-PCR or western blotting.The lentiviral vector pLKO.1-EGFP was used to generate the lentivirus particle CaMKⅡγ-shRNA for transfecting AGS cells.The proliferation of CaMKⅡγ-knocdown AGS cells was tested by the MTT assay.Cell cycle percentage and cell apoptosis were detected by flow cytometry analysis.And the expression of p-STAT3、STAT3 and β-catenin in the transfected cells were determined by Western blotting.In addition,the AGS-shCaMKⅡγ cell xenograft model was established in nude mouse.The tumor volume was measured twice a week and the corresponding proteins expression levels were be detected.Results Tumor tissues showed higher expressions of CaMKⅡγ than the paired peri-tumor tissues with significant difference.The proliferation of transfected AGS-shCaMKⅡγ cells was inhibited significantly compaired with the control cells.The interference of CaMKⅡγ can promote the apotosis of gastric cancer cells.It can also inactivate intracellular STAT signal pathway and Wnt/β-catenin signaling pathway.In the tumor-bearing mouse model,the volume of the tumors generated by the transfected AGS-shCaMKⅡγ cells was smaller than that of the tumors with the control cells.Conclusions Interference of the expression of CaMKⅡγ can effectively inhibit the growth of gastric cancer cells in vitro and in vivo by inducing the apoptosis of gastric cancer cells and inactivating the STAT and Wnt/β-catenin signaling pathway.