Expression Of P2X7 Receptor In Pancreatic Carcinoma And The Mechanismsins In Cell Migration And Invasion

Background:Pancreatic cancer is one of the most common malignant disease,of which the 5-year survival rare is less than 5%.The reason why patients have low rate of resection or mortality is the tumor metastasis when the period of early stage or postoperative.So it's significant that we could find the key molecules to regulate the invasion and metastasis of pancreatic cancer.P2X7 receptor(P2X7R)is an ATP-gate cation channel expressed by wide variety of tumor cell,its activation mediates a larger number of biological processes like cell proliferation,invasion or death because of the unique structure and function.The aim of our study is to detect the P2X7 receptor expression and meaning in pancreatic cancer and furtherly to explore the effects and underlying mechanisms of P2X7 receptor on invasion and migration.Methods:1.The protein and mRNA expressions of P2X7R in pancreatic cancer tissue,paired adjacent carcinoma tissue samples and Human pancreatic cancer cell lines were investigated by immunohistochemical staining and Western blot assay,respectively.2.Human pancreatic cell HPDE6-C7 and Five common human pancreatic cancer cells SW1990?PANC-1?BxPC-3?MiaPaCa-2?PANC02.03 were selected and the P2X7R protein expression was detected in by Western blot and immunofluorescence.Selected pancreatic cancer cells of the P2X7R highly expression,and grouped into:control group,BzATP(200?M)group,BzATP(200?M)+A740003(20?M)group.The transwell assay and wound healing assay was used for investigating cell invasion and migration ability in P2X7R highly expressed pancreatic cancer cells3.To determine the related mechanisms between P2X7R expression and cell invasion or migration,we selected pancreatic cancer cells of the P2X7R highly expression,and grouped into:control group,BzATP(200?M)group,BzATP(200?M)+A740003(20?M)group.Western blot assay were used to detect the protein of E-cadherin?Vimentin?MMP2?MMP9 and the phosphorylation activation of AKTResults:1.The expression level of P2X7R in pancreatic cancer tissues was higher than in the paired adjacent carcinoma tissue.The immunohistochemical staining showed that the positive expression of P2X7R was associated positively with the histological differentiation and lymph node staging(P<0.05).2.The results of transwell assay and wound healing assay showed that the active P2X7R could increase the cell migration and invasion ability of PANC-1 cell line.3.The results of Western blot assay indicated that active P2X7R up-regulated the protein level of MMP2,MMP9,Vimentin and down-regulated the protein level of E-cadherin.ATP time-dependently induced the activation of AKT via P2X7R.Conclusions:1.P2X7R protein was high expression in pancreatic cancer tissues.And it was significantly correlated with tumor histological differentiation and lymph node staging.2.The active P2X7R could increase the cell migration and invasion ability of pancreatic cancer,possibly via activation of AKT pathway and regulation of MMP2,MMP9,Vimentin and E-cadherin expression.Significants:1.The study revealed the relationship between the expressions of P2X7R with the clinicopathologic characteristics of pancreatic cancer tissues,and provided some clues for further study of the progression of pancreatic cancer.2.We verified that P2X7R contributes to the metastasis of pancreatic cancer,and may be a new target in the molecular target therapy of pancreatic cancer.