Abstract |
Gene therapy using an adenoviral vector expressing tumor necrosis factor-alpha (TNF-α) is a new therapeutic approach for pancreatic cancer. However, the efficacy of TNF-α is limited, because it activates nuclear factor-κB (NF-κB). We investigated the combined use of AxCAhTNF-α, adenoviral vector-expressing human TNF-α, and nafamostat mesilate, a serine-protease inhibitor, a NF-κB inhibitor, using pancreatic cancer in mice. In vitro, nafamostat mesilate inhibited TNF-α-induced NF-κB activation and enhanced TNF-α-induced apoptosis in human cancer cell line (MIAPaCa-2). In vivo, we assessed combination treatment of AxCAhTNF-α and nafamostat mesilate using xenograft models in nude mice by subcutaneous injection of MIAPaCa-2. When the implanted tumor size reached 8.0mm, TNF-α group (n=12), was injected AxCAhTNF-α intra-tumorally once a week, while combination group (n=12), was injected AxCAhTNF-α intra-tumorally once a week and nafamostat mesilate intraperitoneally thrice a week. In combination group, tumor growth was significantly slower, and the number of apoptosis cells was significantly greater than those in AxCAhTNF-α group (p<0.05). In conclusion, adenovirus vector-mediated TNF-α gene therapy combined with nafamostat mesilate was effective for pancreatic cancer in mice.
|
Authors | Kenei Furukawa, Toya Ohashi, Koichiro Haruki, Yuki Fujiwara, Tomonori Iida, Hiroaki Shiba, Tadashi Uwagawa, Hiroshi Kobayashi, Katsuhiko Yanaga |
Journal | Cancer letters
(Cancer Lett)
Vol. 306
Issue 1
Pg. 92-8
(Jul 01 2011)
ISSN: 1872-7980 [Electronic] Ireland |
PMID | 21482023
(Publication Type: Journal Article)
|
Copyright | Copyright © 2011 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Benzamidines
- Enzyme Inhibitors
- Guanidines
- NF-kappa B
- Serine Proteinase Inhibitors
- Tumor Necrosis Factor-alpha
- nafamostat
|
Topics |
- Adenoviridae
(genetics)
- Animals
- Benzamidines
- Cell Cycle
- Cell Line, Tumor
- Cell Proliferation
- Enzyme Inhibitors
(pharmacology)
- Gene Transfer Techniques
- Genetic Vectors
- Guanidines
(pharmacology)
- Humans
- Male
- Mice
- Mice, Nude
- NF-kappa B
(metabolism)
- Neoplasm Transplantation
- Pancreatic Neoplasms
(genetics, metabolism)
- Serine Proteinase Inhibitors
(pharmacology)
- Tumor Necrosis Factor-alpha
(genetics)
|