The Effect And Mechanism Of Matrine In Perineural Invasion Of Pancreatic Cancer

Objective:The purpose of this paper is to investigate the effect of matrine on the perineural invasion of pancreatic cancer and its possible mechanism,and to find a new method to inhibit the formation of perineural invasion of pancreatic cancer,so as to provide a possible effective treatment approach for improving the surgical resection rate and prognosis of patients with pancreatic cancer.Methods:1.Using network pharmacology to predict the potential targets of sophora flavescens and matrine to regulate perineural invasion;2.MTT experiment was used to investigate the effect of matrine on the growth and proliferation of pancreatic cancer SW1990cells;Image Pro Plus 6.0 software was used to measure the effect of matrine on DRG axon growth;3.Fluo-3 AM fluorescent probe assay was used to determine the effect of matrine and SW1990 cell culture medium on DRG cells[Ca²⁺]_i;4.Matrigel matrix gel was used to construct an in vitro model of pancreatic cancer perineural invasion to explore the influence of matrine on the in vitro model of pancreatic cancer nerve infiltration.The migration of SW1990 cells and DRG neurite growth in 6 days were observed and photographed,and the nerve invasion index and DRG growth index were measured;5.Gelatinases spectrum and ELISA were used to detect the effects of matrine and DRG on MMP-2 protease and IL-6 and TNF-?expression in SW1990 cellsResults:1.Network pharmacology predicted 38 potential targets of sophora flavescens in regulating perineural invasion,among which MMP-2,IL-6 and TNF were the potential targets of matrine in regulating perineural invasion;2.Matrine had no effect on the growth and proliferation of SW1990 cells when the concentration was less than 0.4mg/mL;3.Matrine with a concentration of 0.4mg/mL or less had no effect on the growth of DRG neurites and[Ca²⁺]_i of DRG cells;4.Compared with the control group,SW1990 cell culture medium significantly increased[Ca²⁺]_i of DRG cells,and matrine at a concentration of 0.4mg/mL significantly inhibited this increase of DRG[Ca²⁺]_i;In vitro models of pancreatic cancer perineural invasion were successfully constructed,in which SW1990 cells and DRG neurite mutually grew,and matrine had a significant inhibitory effect on the perineural invasion index of the pancreatic cancer perineural invasion model in vitro,while had no significant effect on the DRG growth index;5.Gelatinases spectrum and ELISA results showed that matrine significantly reduced the expression of MMP-2 protease and IL-6 in pancreatic cancer SW1990 cells in DRG+matrine group compared with the control group,while there was no significant difference in the expression of TNF-?between each two groups.Conclusion:The results of this study demonstrated that low-dose matrine inhibited the perineural invasion and metastasis of pancreatic cancer in vitro without affecting the growth of pancreatic cancer SW1990 cells and DRG,and the mechanism may be related to the activity and expression of MMP-2 and IL-6 proteins,providing a new strategy for the treatment and prognosis of pancreatic cancer.