ABSTRACT
Pancreatic cancer exhibits a high mortality rate resulting from metastasis and there is currently no effective treatment strategy. Hypoxia serves an important role in cancer cells, where cellular metabolic rate is high. The underlying mechanisms that trigger hypoxia and the invasion of pancreatic cancer cells remain unknown. Investigation of the importance of hypoxia in the invasion of pancreatic cancer cells for potential, novel treatment strategies is of primary concern. Cell Counting Kit8 assay, invasion assay, western blotting and reverse transcriptionquantitative polymerase chain reaction were used to investigate invasion and epithelial mesenchymal transition (EMT) and the expression of Notch1 in MiaPaCa2 cells treated with cobalt II chloride (CoCl2). Hypoxiainducible factor 1α (HIF1α) small interfering (si)RNA and Notch1 inhibitor N[N(3,5Difluorophenacetyl)Lalanyl]Sphenylglycine tbutyl ester (DAPT) were also selected to investigate these mechanisms. Data indicated that CoCl2 increased the invasion ability and altered EMT in MiaPaCa2 cells. CoCl2 regulated the expression of HIF1α and Notch1 in MiaPaCa2 cells. In addition, HIF1α siRNA inhibited the effects of CoCl2 on the expression of Notch1 and decreased Snail, EMT and invasion in MiaPaCa2 cells. DAPT increased the expression of epithelialcadherin and decreased the content of neuralcadherin, Snail and invasion in MiaPaCa2 cells in the presence or absence of CoCl2. CoCl2 promoted invasion by stimulating the expression of HIF1α and regulating the expression of Notch1 and EMT in MiaPaCa2 cells. Targeting the Notch1 signaling molecule may be a novel treatment strategy for the prevention and treatment of pancreatic cancer.
