Objective To study the effect and regulatory mechanism of secreted proteins from PSC on pancreatic ductal adenocarcinoma cells(PANC-1).Methods Conditioned medium(CM)from pancreatic stellate cells(PSC)was collected through an indirect co-culture method,and PANC-1 cells were cultured separately with CM for 0,2,and 24 h.The proliferation phenotype of PANC-1 cells under different stimulation periods was detected u-sing the CCK-8 assay.Proteomic analysis was performed to analyze the changes in protein levels of PANC-1 cells,and the most significant protein changes were validated using Western blot.Results Compared with the control group,the proliferation rate of PANC-1 cells increased after being stimulated by PSC derived CM;The results of proteomic analysis showed that the protein expression of metabolic pathways in PANC-1 cells increased continuously after being cultured in PSC CM for 0,2,and 24 h.Western blot analysis confirmed an increasing trend of PIK3C2A in PANC-1 cells,indicating that the CM from PSC might promote the proliferation of PANC-1 cells by upregulating the expression of PIK3C2A.Conclusion The CM of PSC may promote the proliferation of PANC-1 cells by upregulating the expression of PIK3C2A,which improves the understanding of the mechanism of interaction between PSCs and pancreatic cancer cells in the tumor microenvironment.