Abstract:Objective: To investigate the effect and mechanism of fibroblast growth factor 21 (FGF21) on the proliferation and activation of stellate cells in the inflammatory environment of pancreatic cancer cells. Methods: The appropriate time to establish an inflammatory microenvironment was determined by RT-qPCR to detect interleukin (IL) -6 and IL-8 mRNA expression level of cholecystokinin (CCK) on human pancreatic cancer cells (PCC) such as Capan-1 and MIA PaCa-2. PCC (Capan-1, MIA PaCa-2) CCK supernatant and PCC (Capan-1, MIA PaCa-2) CCK+FGF21 supernatant were acted on human pancreatic stellate cells (PSC). CCK-8 and Western blot were used to detect the effect of each group’s supernatant on the activity of pancreatic stellate cells and the expression of α-smooth muscle protein (α-SMA), a marker of activation. RT-qPCR and Western blot were used to detect the effect of FGF21 on the expression of PCC EGR1 and PDGFB mRNA and protein after CCK treatment. Western blot further detected the effect of AMPK inhibitor (compound C) added to PCC CCK group and PCC CCK+FGF21 group on the expression of p-AMPK and EGR1 protein in AMPK-κB signaling pathway. Results: The relative expressions of IL-8 mRNA in Capan-1 6 h group and in MIAPaCa-2 24 h group treated with CCK were significantly higher than those in other groups (P<0.05). Compared with the PCC CCK supernatant group, the PCC CCK+FGF21 supernatant group had significantly inhibited the proliferation of PSC cells (P<0.05), the expression of α-SMA protein was significantly reduced (P<0.001). Intervention with FGF21, EGR1, PDGFB mRNA and protein expressions were significantly lower than those in CCK group (P<0.05). After compound C was added to the PCC CCK+FGF21 group, the expression level of p-AMPK protein decreased (P<0.01), and the expression level of EGR1 protein expression increased (P<0.05). Conclusion: FGF21 may prevent tumor by inhibiting the proliferation and activation of stellate cells in the inflammatory environment of pancreatic cancer cells and the mechanism may be related to its activation of the AMPK pathway of pancreatic cancer cells in the inflammatory environment, down-regulation of EGR1 expression and reduction of PDGFB expression.
