Interferon-alpha in combination with chemotherapy has potent antiangiogenic properties in an orthotopic mouse model for pancreatic adenocarcinoma.

Department of Surgery, National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.

There are clinical data showing encouraging results for combining chemoradiotherapy with interferon (IFN)-alpha (CapRI scheme) for the treatment of pancreatic carcinoma. Here, it was tried to evaluate the antiangiogenic effect of IFN-alpha in combination with chemotherapy. Mice were inoculated with syngeneic pancreatic carcinoma cells in the pancreas. After 5 days, the animals were treated with 5-fluorouracil (5-FU)+/-IFN-alpha. Tumor growth, vascular endothelial growth factor (VEGF) serum levels and VEGF-R expression, real-time reverse transcription-polymerase chain reaction of mRNA coding for RGS-5, an angiogenic pericyte marker at sites of physiologic and pathologic angiogenesis and impact of IFN-alpha treatment on vessel density by CD31 stain and intravital microscopy were analyzed. The addition of IFN-alpha to 5-FU-treatment decreased tumor volume, reduced serum level of VEGF, and down-regulated the expression of VEGF-receptor significantly. Furthermore, the combination therapy revealed a decrease in vessel density and a down-regulation of RGS-5, which is a protein involved in angiogenic tumor vasculature. IFN-alpha significantly improves the outcome of 5-FU-therapy in treating pancreatic carcinoma. This is at least partly mediated by IFN-alpha antiangiogenic properties, which acts along with 5-FU on the VEGF system, vessel density, and RGS-5 expression in pericytes.

PMID: 18157009 [PubMed - indexed for MEDLINE]