Redox Regulation of Pancreatic Cancer Cell Growth: Role of Glutathione Peroxidase in the Suppression of the Malignant Phenotype
| Autor: | Christine J. Weydert, Justine M. Ritchie, Marilyn M. Hinkhouse, Joseph J. Cullen, Wenqing Sun, Jingru Liu, Larry W. Oberley |
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| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Pancreatic disease Tumor suppressor gene Genetic Vectors Adenoviridae Mice chemistry.chemical_compound Cell Line Tumor Internal medicine Pancreatic cancer Genetics medicine Animals Humans Molecular Biology chemistry.chemical_classification Glutathione Peroxidase biology Superoxide Dismutase Glutathione peroxidase Gene Transfer Techniques Cancer medicine.disease Pancreatic Neoplasms Phenotype Endocrinology chemistry Cell culture biology.protein Cancer research Molecular Medicine Growth inhibition Oxidation-Reduction Cell Division Peroxidase |
| Zdroj: | Human Gene Therapy. 15:239-250 |
| ISSN: | 1557-7422 1043-0342 |
| DOI: | 10.1089/104303404322886093 |
| Popis: | Pancreatic cancer has low levels of antioxidant enzymes including manganese superoxide dismutase (MnSOD), which converts superoxide radical (O(2)(*-)) into hydrogen peroxide (H(2)O(2)), and glutathione peroxidase (GPx), which converts H(2)O(2) into water. Recent studies have demonstrated that overexpression of MnSOD has a tumor-suppressive effect in pancreatic cancer. However, GPx overexpression has been shown to reverse the tumor cell growth inhibition caused by MnSOD overexpression in other types of cancer. Our aims were to determine if overexpression of GPx alters in vitro pancreatic cancer cell behavior and if delivering the GPx gene directly to tumor xenografts alters growth and survival. In vitro, AdGPx slowed tumor growth by 39% and AdMnSOD slowed tumor growth by 35%. AdGPx also decreased plating efficiency and growth in soft agar. The combination of AdGPx and AdMnSOD had the greatest effect on tumor cell growth suppression with a 71% reduction in cell growth compared to controls. In vivo, either AdGPx or AdMnSOD alone slowed tumor growth by 51% and 54%, respectively, while the combination of AdGPx and AdMnSOD potentiated tumor growth suppression by 81% of controls and increased animal survival. GPx may be a tumor suppressor gene in pancreatic cancer. Delivery of the GPx gene alone or in combination with the MnSOD gene may prove beneficial for treatment of pancreatic cancer. |
| Databáze: | OpenAIRE |
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