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Journal of Oncology
Volume 2010 (2010), Article ID 178174, 10 pages
http://dx.doi.org/10.1155/2010/178174
Research Article

Use of H19 Gene Regulatory Sequences in DNA-Based Therapy for Pancreatic Cancer

1Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond Safra Campus, Givat Ram, Jerusalem 91904, Israel
2Department of Pathology, Hadassah University Hospital, Jerusalem 91120, Israel
3Institut National de la Santé et de la Recherche Médicale U531, Institut Louis Bugnard, Institut Federatif de Recherche-31, Centre Hospitalier Universitaire Rangueil, 31403 Toulouse, France
4Department of Surgery “A”, Sheba Medical Center, Tel Hashomer 52621, Israel

Received 22 June 2010; Accepted 13 September 2010

Academic Editor: Douglas S. Tyler

Copyright © 2010 V. Scaiewicz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Pancreatic cancer is the eighth most common cause of death from cancer in the world, for which palliative treatments are not effective and frequently accompanied by severe side effects. We propose a DNA-based therapy for pancreatic cancer using a nonviral vector, expressing the diphtheria toxin A chain under the control of the H19 gene regulatory sequences. The H19 gene is an oncofetal RNA expressed during embryo development and in several types of cancer. We tested the expression of H19 gene in patients, and found that 65% of human pancreatic tumors analyzed showed moderated to strong expression of the gene. In vitro experiments showed that the vector was effective in reducing Luciferase protein activity on pancreatic carcinoma cell lines. In vivo experiment results revealed tumor growth arrest in different animal models for pancreatic cancer. Differences in tumor size between control and treated groups reached a 75% in the heterotopic model ( ) and 50% in the orthotopic model ( ). In addition, no visible metastases were found in the treated group of the orthotopic model. These results indicate that the treatment with the vector DTA-H19 might be a viable new therapeutic option for patients with unresectable pancreatic cancer.