omeprazole inhibits proliferation and modulates autophagy in pancreatic cancer cells奥美拉唑抑制和调节自噬在胰腺癌细胞增殖.pdfVIP

Omeprazole Inhibits Proliferation and Modulates Autophagy in Pancreatic Cancer Cells 1 ¤a 2 2 3 4 Andrej Udelnow * , Andreas Kreyes , Stefan Ellinger , Katharina Landfester , Paul Walther , Thomas 5 5 1 1. ¨ 1.¤b Klapperstueck , Johannes Wohlrab , Doris Henne-Bruns , Uwe Knippschild , Peter Wurl 1 Department of General, Visceral and Transplantation Surgery, University Hospital of Ulm, Ulm, Germany, 2 Institute of Organic Chemistry, Macromolecular Chemistry and Organic Materials, University of Ulm, Ulm, Germany, 3 Max Planck Institute for Polymer Research, Mainz, Germany, 4 Department of Electron Microscopy, University of Ulm, Ulm, Germany, 5 Department of Dermatology and Venereology, Martin Luther University of Halle-Wittenberg, Halle, Germany Abstract Background: Omeprazole has recently been described as a modulator of tumour chemoresistance, although its underlying molecular mechanisms remain controversial. Since pancreatic tumours are highly chemoresistant, a logical step would be to investigate the pharmacodynamic, morphological and biochemical effects of omeprazole on pancreatic cancer cell lines. Methodology/Principal Findings: Dose-effect curves of omeprazole, pantoprazole, gemcitabine, 5-fluorouracil and the combinations of omeprazole and 5-fluorouracil or gemcitabine were generated for the pancreatic cancer cell lines MiaPaCa- 2, ASPC-1, Colo357, PancTu-1, Panc1 and Panc89. They revealed that omeprazole inhibited proliferation at probably non- toxic concentrations and reversed the hormesis phenomena of 5-fluorouracil. Electron microscopy showed that omepr