Effect Of Hypoxia On Invasion And Migration Of Pancreatic Cancer Cells And Its Mechanism

Objectives To investigate the effects of hypoxia on the migration and invasion ability,epithelial-mesenchymal transformation,extracellular matrix,and Hippo signaling pathway of pancreatic cancer PANC-1 cells,to investigate the effect of silencing HIF-1α on the invasion and migration of pancreatic cancer cells and the mechanism of action,and to provide a theoretical basis for further prevention and treatment of pancreatic cancer.Methods 1.The PANC-1 cells of pancreatic cancer were divided into control group and hypoxic group.The cells were cultured for 24 hours under normal oxygen(5%CO2,95%O2)and hypoxia(5%CO2,2%O2,93%N2)conditions respectively.The expression levels of emt-related proteins,MMP2,MMP-9,and Hippo signaling pathways were detected by Western blot and q RT-PCR.2.The PANC-1 cells were divided into control group,hypoxic group,hypoxic idle-transfer group and hypoxic interference group.Si RNA HIF-1 were transfected into pancreatic cancer cells by liposome transient transfection,and the transfection effect was detected by Western blot.Cell scratch and Transwell chamber were used to detect the changes of migration and invasion ability of pancreatic cancer cells.Western blot was used to detect the expression levels of emt-related proteins and related proteins in MMP2,MMP-9 and Hippo signaling pathways.3.SPSS22.0 was used for t test and One-Way anova,and P<0.05 indicated that the difference was statistically significant.Results 1.The hypoxic group,(1)the scratch area,number of migrating cells and number of invading cells were higher than those in the control group,with statistically significant differences(P<0.05).(2)the expression levels of e-cadherin protein and m RNA were lower than those of the control group,with statistically significant differences(P<0.05).(3)the expression levels of Vimentin protein and m RNA were higher than those of the control group,and the difference was statistically significant(P<0.05).(4)the expression levels of mmp-2 and mmp-9 proteins and m RNA were higher than those of the control group,with statistically significant differences(P<0.05).(5)the expression levels of TEAD proteins were higher than those of the control group,while the expression levels of p YAP proteins were lower than those of the control group,with statistically significant differences(P<0.05).2.Compared with the control group,the expression levels of HIF-1α protein in the anoxia group and idling group were higher than those in the control group,and the hif-1 protein levels in the anoxia interference group were lower than those in the control group,with statistically significant differences(P<0.05).3.Hypoxic interference group :(1)the scratch area,number of migrating cells and number of invading cells were lower than that of hypoxic idling group,with statistically significant differences(P<0.05).(2)the expression level of e-cadherin protein was higher than that of the hypoxic group,and the expression level of Vimentin protein was lower than that of the hypoxic group,with statistically significant differences(P<0.05).(4)the protein expression levels of MMP-2 and mmp-9 were lower than that of the hypoxic idling group,and the difference was statistically significant(P<0.05).(5)there was no statistically significant difference in the expression levels of TEAD and p YAP proteins between the hypoxic idleness group and the hypoxic idleness group(P>0.05).Conclusions1.Hypoxia can promote the invasion and migration of pancreatic cancer cells and enhance the high expression of hif-1 in pancreatic cancer cells,which may be realized by affecting the of EMT,MMPs and Hippo signaling pathways.2.Silencing HIF-1αexpression under hypoxia can reduce the invasion and migration of pancreatic cancer cells.Silencing of hif-1 expression may be possible through the invasion and migration capacity of EMT and MMPs in pancreatic cancer.Figure15;Table11;Reference 155...