Clinical Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 14, 2005; 11(10): 1521-1528
Published online Mar 14, 2005. doi: 10.3748/wjg.v11.i10.1521
Synergistic effects of interferon-alpha in combination with chemoradiation on human pancreatic adenocarcinoma
Jian-Hua Ma, Emilia Patrut, Jan Schmidt, Hanns-Peter Knaebel, Markus W. Büchler, Angela Märten
Jian-Hua Ma, Emilia Patrut, Jan Schmidt, Hanns-Peter Knaebel, Markus W. Büchler, Angela Märten, Department of Surgery, University of Heidelberg, Germany
Author contributions: All authors contributed equally to the work.
Supported by a Generous Grant From the Joachim-Siebeneicher-Foundation
Correspondence to: Angela Märten, Department of Surgery, Univerity of Heidelberg, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany. angela.maerten@med.uni-heidelberg.de
Telephone: +49-6221-56-39890 Fax: +49-6221-56-8240
Received: August 25, 2004
Revised: August 27, 2004
Accepted: September 1, 2004
Published online: March 14, 2005
Abstract

AIM: To determine whether IFN-α is the agent that turns a slightly effective treatment (radiochemotherapy) into a potent therapy, we tested IFN-α for its synergistic properties.

METHODS: Eight pancreatic carcinoma cell lines were treated with the single agents and combinations of these. The role of IFN-α regarding a) direct inhibitory effects; b) radio and chemosensitizing effects; c) anti-angiogenic properties and d) enhancement of immunogenicity was investigated.

RESULTS: Our results show that IFN-α has direct inhibitory properties and some synergistic influence as determined by AnnexinV/PI stain and cell count. IFN-α is also able to prevent the increase in proliferation rate and VEGF secretion of CDDP resistant cells. Having taken the results from immunogenicity experiments together, we found cells that can be influenced by IFN-α but were less susceptible against T cells. Furthermore, high expression of MHC molecules, CD118, EGF-R and Fas was predictive for a good response.

CONCLUSION: In conclusion, IFN-α has direct cytotoxic effects, acts as a radiosensitizer and circumvents tumor cell-regrowth after CDDP treatment. These mechanisms may be responsible for the good clinical outcome of CapRI.

Keywords: Interferon-alpha; Pancreatic adenocarcinoma; Synergistic effects; Combination therapy