〔Abstract〕 Objective To explore the impact of high glucose(HG) intervention on immune escape of pancreatic cancer cells and its molecular mechanisms. Methods PANC-1 cells were treated with different concentrations of glucose(0,7.5,15,30 mmol/L) for 24 h to establish high glucose intervention PANC-1 cells.miR-429 mimics and its negative control(mimics NC) were transfected into PANC-1 cells, which were divided into control group, HG group, HG+mimics NC group, HG+mimics group, HG+mimics+oe-NC group, and HG+mimics+oe-ZEB1 group.Flow cytometry was utilized to measure the expression level of cell surface molecule PD-L1;qRT-PCR was used to detect the expression levels of miR-429 and ZEB1 mRNA in cells; Western blot was used to detect the expression level of ZEB1 protein in cells.The above-mentioned PANC-1 cells from each group were co-cultured with CD8+T cells to establish a co-culture system, and CCK-8 was used to assess cell proliferation activity; apoptosis levels of cells were measured using flow cytometry; lactate dehydrogenase(LDH) release assay was used to detect the killing effect of CD8+T cells on PANC-1 cells; dual-luciferase reporter system was used to validate the target-regulatory relationship between miR-429 and ZEB1. Results HG could promote the expression of cell surface molecules PD-L1 and ZEB1 in PANC-1 cells(P<0.05),inhibit the expression of miR-429,and exhibit concentration dependence.Overexpression of miR-429 could significantly suppress the expression of cell surface molecule PD-L1 induced by HG in PANC-1 cells, while overexpression of ZEB1 could reverse the inhibitory effect of miR-429 overexpression on the expression of cell surface molecule PD-L1 induced by HG.After establishing a co-culture system with CD8+T cells, compared with the control group, the proliferation activity of PANC-1 cells in the HG group significantly increased, and the apoptosis rate and cytotoxicity significantly decreased(P<0.05).Compared with the HG+mimics NC group, the proliferation activity of PANC-1 cells in the HG+mimics group significantly decreased, and the apoptosis level and cytotoxicity significantly increased(P<0.05).Compared with the HG+mimics group, the proliferation activity of PANC-1 cells in the HG+mimics+oe-ZEB1 group significantly increased, and the apoptosis rate and cytotoxicity significantly decreased(P<0.05).Dual luciferase reporter gene assay confirmed that miR-429 negatively regulated ZEB1. Conclusion High glucose promotes immune escape of PANC-1 cells by downregulating the expression level of miR-429,negatively regulating the expression of ZEB1 mRNA,and increasing the expression level of cell surface molecule PD-L1 in PANC-1 cells.