Effects Of Atic On Proliferation And Migration Of Pancreatic Cancer Cells And Its Related Mechanisms

Objective:The Pur Pose of this study was to investigate the ex Pression of ATIC in Pancreatic cancer and its effects on the Proliferation and migration of Pancreatic cancer cells as well as the AKT/mTOR signaling Pathway.Methods:(1)The m RNA ex Pression of ATIC in Pancreatic cancer,the relationshi P between ATIC and Prognosis of Patients with Pancreatic cancer,and the correlation between ATIC and clinico Pathologic features of Patients with Pancreatic cancer were analyzed by using TCGA and GEPIA databases.(2)The exPression of ATIC in normal Pancreatic ductal ePithelial cells(H6C7)and other Pancreatic cancer cells was detected by real-time quantitative PCR(q RT-PCR)and Western Blot,and the cell lines were selected for subsequent tests.(3)Lentivirus transfection technique was used to construct knockdown and overex Pression stable strains of Pancreatic cancer cells,and the knockdown or overex Pression effects were verified by q RT-PCR and Western Blot.The effects of ATIC on the Proliferation and migration of Pancreatic cancer cells were investigated by CCK8 assay,Plate cloning assay,cell scratch assay and Transwell assay.(4)The influence of ATIC on e Pithelial mesenchymal transformation(EMT)and related indexes as well as AKT/mTOR signaling Pathway Proteins was detected by Western Blot.Results:(1)The results of biological information database showed that the exPression level of ATIC in Pancreatic cancer tissues was higher than that in adjacent tissues.According to GEPIA database analysis,ATIC is highly ex Pressed in Pancreatic cancer.According to the TCGA database,the disease-s Pecific survival and overall survival of Pancreatic cancer Patients with high ex Pression of AITC were lower than those of ATIC Patients with low ex Pression.The ROC curve Predicted the Predictive effect of ATIC in Pancreatic cancer.The results showed that ATIC could well Predict the occurrence of Pancreatic cancer with high sensitivity and s Pecificity.The database was used to analyze the correlation between ATIC and the clinico Pathologic features of Pancreatic cancer Patients,and the results showed that ATIC was closely related to the main treatment outcomes and Pathological grades.(2)The ex Pression of ATIC in normal Pancreatic ductal e Pithelial cells(H6C7)and other Pancreatic cancer cells was detected by q RT-PCR and Western Blot.The results showed that the ex Pression level of ATIC in Pancreatic cancer cells was higher than that in normal Pancreatic ductal e Pithelial cells,and cell lines were selected for subsequent tests.(3)Lentivirus transfection technique was used to construct knockout and overex Pression cell lines of Pancreatic cancer cells,and the knockout or overex Pression effect was detected by Western Blot method and q RT-PCR method,and stable metastases were constructed for subsequent tests.The effects of ATIC on the Proliferation and migration function of Pancreatic cancer cells were studied by CCK8 assay,Plate cloning assay,cell scratch assay and Transwell assay.The Proliferation and migration ability of PANC-1 and PATU-8999 cells of Pancreatic cancer were inhibited after knockout of ATIC,but after overex Pression of ATIC,The Proliferation and migration of PANC-1 and PATU-8999 cells of Pancreatic cancer were enhanced.(4)After knockout of ATIC,EMT and related Proteins changed,the ex Pressions of E-cadherin and Cas Pase-3 were u P-regulated,while the ex Pressions of N-cadherin,Vimentin,Snail and Pcna were down-regulated.After overex Pression of ATIC,the ex Pressions of E-cadherin and Cas Pase-3 were down-regulated.N-cadherin,Vimentin,Snail and Pcna were u P-regulated.In addition,in the AKT/mTOR signaling Pathway,the ex Pressions of AKT and mTOR are not significantly different after ATIC knockdown,while the ex Pressions of P-AKT and P-mTOR are inhibited.On the contrary,after ATIC overex Pression,the ex Pressions of AKT and mTOR are still not significantly different,while the ex Pressions of P-AKT and P-mTOR are uP-regulated.Conclusion:(1)ATIC is highly ex Pressed in Pancreatic cancer and affects the Prognosis of Patients with Pancreatic cancer.(2)ATIC knockdown inhibited the Proliferation and migration of Pancreatic cancer cells,and ATIC overex Pression enhanced the Proliferation and migration of Pancreatic cancer cells.(3)ATIC Promotes the Proliferation,migration and EMT Process of Pancreatic cancer cells by regulating AKT/mTOR signaling Pathway.