The Role And Mechanism Of NDRG3 In Gastric Cancer

Objective:To detect the difference of NDRG3 expression in human gastric cancer and adjacent non-cancerous tissues and different gastric cancer cell lines,explore the significance of NDRG3 in the progress of gastric cancer.To provide new ideas for molecular diagnosis and targeted therapy of human gastric cancer.Methods:In the Oncomine database,the differences of NDRG3 expression in the tissues of gastric cancer and the corresponding expression levels of m RNA in the adjacent tissues were examined.And the data were collected to plot the overall survival rate of gastric cancer patients between NDRG3 overexpression and low expression.The expression of NDRG3 mRNA and protein in 127 cases of gastric cancer and the corresponding adjacent tissues were detected by qRT-PCR and immunohistochemistry.The correlation between NDRG3 expression and clinicopathological factors of gastric cancer was analyzed.Western blot was used to compare the expression of NDRG3 in gastric cancer cell lines.The expression of pcDNA-NDRG3 was transfected with SGC-7901 cells.The effect of overexpression was evaluated by Western blot.The growth and migration of gastric cancer cells were evaluated by CCK-8 proliferation assay and transwell migration assay.EMT was detected by Western blot.Protein changes.The expression of ERK1 / 2,PI3 K /AKT pathway protein was detected at the protein level.The expression of NDRG3 in MGC-803 gastric cancer cells was inhibited by NDRG3 siRNA.The effect of NDRG3 on the proliferation of gastric cancer cells was evaluated by platelet clone formation assay,CCK-8 proliferation assay,transwell migration,apoptosis and cell cycle test.And the expression of EMT,invasion and metastasis,apoptosis and other related proteins were detected by Western blot.The expression of ERK1 / 2,PI3 K /AKT related proteins was confirmed by Western blot,and the mechanism of NDRG3 in gastric carcinoma was explored.Results:1.The expression of NDRG3 in gastric cancer tissues was higher than that in adjacent tissues(P <0.05).The results of immunohistochemistry showed that NDRG3 was highly expressed in gastric cancer cells(cytoplasm and nucleus).The expression level of NDRG3 protein in most gastric cancer cells was higher than that in normal gastric epithelial cells(GES-1),which was consistent with that in the database.The overall survival rate of patients with high expression of NDRG3 in gastric cancer was lower than that in patients with low expression of NDRG3.2.The results of CCK8 proliferation assay showed that the migration ability and proliferation ability of SGC-7901 gastric cancer cells overexpressing NDRG3 significantly increased the expression of E-cadherin,increased the expression of N-cadherin and ?-catenin,promoted the occurrence of EMT;Timp1 expression decreased,MMP9 expression increased,and promote the invasion and metastasis of the tumor.3.The expression of NDRG3 in MGC-803 cells was inhibited,which inhibited the cell cloning,migration and proliferation,and promoted the apoptosis of gastric cancer cells.E-cadherin expression increased,N-cadherin expression increased,inhibition of EMT;Timp1 expression increased,inhibition of tumor invasion and metastasis;PCNA expression decreased,inhibition of tumor cell growth;Bcl2L1expression decreased Cleaved-caspase 8,Cleaved caspase 3,Cleaved PARP expression enhanced,and promote apoptosis of gastric cancer cells.ERK1 / 2,PI3K/ AKT-related pathways,p-ERK1 / 2,p-AKT,PI3 K were significantly reduced.Conclusions:NDRG3 is involved in the development and progression of gastric cancer.It may induce EMT to promote the metastasis and growth of gastric cancer cells by activating ERK1 / 2 and PI3 K / AKT pathway,and inhibit the apoptosis of tumor cells.NDRG3 will serve as a new molecular diagnostic indicator of gastric cancer,and thus provide a new basis for clinical treatment of gastric cancer.