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World J Gastroenterol. Jun 28, 2014; 20(24): 7914-7925
Published online Jun 28, 2014. doi: 10.3748/wjg.v20.i24.7914
Published online Jun 28, 2014. doi: 10.3748/wjg.v20.i24.7914
Distinct antifibrogenic effects of erlotinib, sunitinib and sorafenib on rat pancreatic stellate cells
Anne Elsner, Falko Lange, Brit Fitzner, Robert Jaster, Department of Medicine II, Division of Gastroenterology, University Medicine Rostock, 18057 Rostock, Germany
Brit Fitzner, Department of Neurology, University Medicine Rostock, 18119 Rostock, Germany
Martin Heuschkel, Bernd Joachim Krause, Department of Nuclear Medicine, University Medicine Rostock, 18057 Rostock, Germany
Author contributions: Elsner A and Lange F contributed equally to this work; Jaster R and Krause BJ designed the study; Elsner A, Lange F, Fitzner B and Heuschkel M performed the experiments; all authors analyzed the data; and Jaster R wrote the manuscript.
Supported by Grant from the Deutsche Forschungsgemeinschaft (to RJ)
Correspondence to: Robert Jaster, MD, Department of Medicine II, Division of Gastroenterology, University Medicine Rostock, E.-Heydemann-Str. 6, 18057 Rostock, Germany. jaster@med.uni-rostock.de
Telephone: +49-381-4947349 Fax: +49-381-4947482
Received: December 19, 2013
Revised: March 14, 2014
Accepted: April 8, 2014
Published online: June 28, 2014
Revised: March 14, 2014
Accepted: April 8, 2014
Published online: June 28, 2014
Core Tip
Core tip: There are no specific therapies available to treat pancreatic fibrosis, a key feature of chronic pancreatitis and pancreatic cancer. Here we show that three clinically available small molecule kinase inhibitors (SMI), erlotinib, sunitinib and sorafenib, exert antifibrogenic effects in vitro by inhibiting key functions of rat pancreatic stellate cells (PSC), the main source of extracellular matrix proteins in the diseased pancreas. Furthermore, additive effects of the drugs were observed. Our studies also provide insight into molecular mechanisms of SMI action in PSC. We suggest that the antifibrotic efficiency of SMI, especially sorafenib, should be further evaluated in preclinical studies.