Expression of snail in pancreatic cancer promotes metastasis and chemoresistance

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 that 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. Materials, 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. (c) 2007 Elsevier Inc. All rights reserved.