Preliminary Study On Expression And Biological Role Of Sortilin In Pancreatic Cancer

Purpose:To investigate the differential expression of sortilin in pancreatic cancer and its adjacent tissues,and to analyze its correlation with clinical indicators and patient survival rate;to explore the proliferation,invasion and migration of pancreatic cancer cells(Bxpc3,Capan1)after siRNA targeted inhibition of sortilin and the molecular biological mechanism of these phenomena.Methods:the res?lts of IHC were statistically analyzed.The effective siRNA targeting fragment was screened by RT-PCR and verified by Western blot.After knocking down sortilin,CCK8 was used to detect the proliferation of pancreatic cancer cells.Transwell invasion test was used to detect the invasion of cells.Cell scratch test was used to detect the migration of cells Finally,P53,NF?B and MMP9 were detected at mRNA and protein levels,and the role of sorilin in the pathogenesis of pancreatic cancer was analyzed.Results:the expression of sortilin in pancreatic cancer and paracancerous cell nucleus was different(P<0.05),but the expression of sortilin in cytoplasm was not statistically significant(P=0.897);The pathological grade in the clinicopathological characteristics of patients with pancreatic cancer is only related to the expression of sortilin in the tissue cytoplasm;Univariate analysis showed that the expression of sortilin in tissue cytoplasm(P=0.019),pathological grade(P=0.048),clinical stage(P=0.020),M stage(P=0.015)were correlated with the prognosis of patients,Multivariate analysis indicated that only the expression level of sortilin in tissue cytoplasm(P=0.026)can be used as an independent factor to judge prognosis;Two pancreatic cancer cells,Bxpc3 and Capanl,were transfected with siRNA,and the cells were inhibited by siRNA-B(P=0.0022)and siRNA-C(P=0.0043).After knocking down sortilin,CCK8 experiment showed that the proliferation of Bxpc3(P<0.0001)and Capanl(P<0.0001)cells was inhibited,while Transwell experiment showed that the invasiveness of both cells decreased(P=0.0057)and Bxpc3(P=0.0006);The scratch test showed that the migration ability of the two cells was also inhibited Capan1(P=0.1251),Bxpc3(P=0.7791);Both cells showed an upgration in P53(Capan1 P=0.002,Bxpc3P=0.006),while degration in NF?B(Capanl P=0.002,Bxpc3P=0.000)and MMP9(Capanl P=0.000,Bxpc3P=0.002)at the mRNA and protein levels.Conclusion:Sortilin is upregulated in the nucleus of pancreatic cancer tissue.Its expression in the cytoplasm of pancreatic cancer tissue is inversely proportional to the malignant degree of pancreatic cancer in patients.The higher the expression level of sorin,the lower the malignant degree of pancreatic cancer and the better the prognosis of the patient.Sortilin knockdown at the cellular level can affect the proliferation,invasion,and metastasis of pancreatic cancer cells.These phenomena may be related to the regulatory pathways of sortilin at the tissue and cell levels.At the cellular level,the proliferation of pancreatic cancer cells may be regulated by the soritlin/P53/NF?B pathway,and the invasion and migration of pancreatic cancer cells may be regulated by the sortilin/MMP9 pathway.The regulatory pathway at the tissue level needs further study.