| Background Pancreatic cancer is a dreadful malignancy. Because of its tendency to metastasis and its resistance to chemotherapy, the prognosis remains poor. Snail is a transcriptional factor which endows epithelial cells with migratory and anti-apoptotic abilities. Its expression has been demonstrated in many tumors. We hypothesized that Snail may be expressed in pancreatic cancer, and it may confer invasive and chemoresistant properties.Material, Methods, and results We immunohistochemically examined Snail expression in pancreatic cancer, and found that it was expressed in 20 of 56 (36%) samples of pancreatic cancer. The Snail expression had a close correlation with lymph node invasion and distant metastasis. After transfecting Snail cDNA into pancreatic cancer cell line Panc-1, we found that Snail triggered overt epithelial to mesenchymal transitions in Panc-1 cells. The tumor invasive ability in vitro was evaluated using a transwell invasive chamber. Snail dramatically promoted the invasive ability of Panc-1 cells. Chemosensitivity of Panc-1 cells to 5-fluorouracil or gemcitabine after Snail transfection was assayed by MTT cell proliferation assay. Overexpression of Snail enhanced the chemoresistance to 5-fluorouracil of gemcitabine at different dosages. Moreover, Snail transfected Panc-1 cells produced more spontaneous metastasis than parental untransfected cells after orthotopically injected into the pancreas of nude mice.Conclusion Snail is expressed in pancreatic cancer; it confers enhanced invasive ability and chemoresistance to pancreatic cancer cells. Snail may be a marker for predicting the malignancy of pancreatic cancer. Further therapy target to Snail may be of great benefit to pancreatic cancer patients. Objective To investigate the occurrence of EMT in pancreatic cancer and the expression of epithelial marker E-cadherin, mesenchymal marker vimentin in pancreatic cancer and its correlation with the malignant features.Methods Snail,E-cadherin,vimentin expression were determined in 56 cases of human pancreatic carcinoma with immunohistochemistry and the results were compared with pathology. Western blot and immunofluorescence were performed to compare the expression of E-cadherin, vimentin, Snail in different pancreatic cancer cells: Miapaca-2, Panc-1 and BxPc-3. Transwell invasion assay was performed to compare the in vitro invasive abilities of different cancer cells.Results Reduced expression of E-cadherin was found in 26 cases, vimentin, a mesenchymal marker, was found to be highly expressed in pancreatic cancer cells in 6 cases. Significant correlation was detected between the expression of Snail and the reduced expression of E-cadherin and the expression of vimentin. The expression of vimentin was high in Miapaca-2 pancreatic cancer cells and the E-cadherin was low, but the invasive ability was strong. There were no vimentin and Snail expression in BxPc-3 cells, but the E-cadherin expression was strong and the invasive ability was weak.Conclusion Represson of epithelial marker and accquistion of mesenchymal marker may be involved in the progression of pancreatic cancer. Re-expression of Snail in pancreatic cancer may accelerate invasion through epithelial to mesenchymal transition. Epithelial to mesenchymal transition may be mechanisms for pancreatic cancer cells to acquire the invasive ability. Objective To investigate whether hypoxia environment can induce epithelial to mesenchymal transition of pancreatic cancer cells and the potential mechanisms.Methods The pancreatic cancer cells Panc-1 was cultured in hypoxia environment. After cultured for indicated periods, the in vitro invasive ability of Panc-1 cells was compared with normoxia group using Transwell invasion assay. The epithelial marker E-cadherin and the mesenchymal marker vimentin were assayed by Western blot. The Snail mRNA was assayed by realtime PCR. To elucidate the potential mechanisms involved in the phenotypic changes of Panc-1 cells in hypoxia environment, the plasmid pGenesil-1-HIF-1αexpressing siRNA targeting at HIF-1αgene and the control plasmid was transient tansfected into the Panc-1 cells and were cultured for indicated times. Then, Western blot was performed to detect the changes of epithelial marker E-cadherin and the mesenchymal marker vimentin. The expression of Snail mRNA was detected by RT-PCR. The invasive abilities invtro was detected by Transwell invasion assay.Results The invasive ability was increased dramatically in hypoxia environment. Hypoxia repressed the expression of E-cadherin, and enhanced the vimentin expression. Besides, the Snail mRNA was increased in hypoxia environment. After silencing the expression of HIF-1αof Panc-1 cells in hypoxia environment, the expression of E-cadherin can be enhanced,the vimentin, Snail expression was decreased. The invasive abilities of Panc-1 cells in hpoxia environment was repressed greatly accordingly.Conclusion Hypoxia can activate the HIF-1αexpression which can induce the Snail transcriptional factor and trigger epithelial to mesenchymal transition.
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