Redox regulation of pancreatic cancer cell growth: Role of glutathione peroxidase in the suppression of the malignant phenotype

Jingru LIU; Marilyn M HINKHOUSE; Wenqing Sun; Christine J WEYDERT; Justine M RITCHIE; Larry W OBERLEY; Joseph J CULLEN

doi:10.1089/104303404322886093

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Redox regulation of pancreatic cancer cell growth: Role of glutathione peroxidase in the suppression of the malignant phenotype

Journal article

Peer reviewed

Redox regulation of pancreatic cancer cell growth: Role of glutathione peroxidase in the suppression of the malignant phenotype

Jingru LIU, Marilyn M HINKHOUSE, Wenqing Sun, Christine J WEYDERT, Justine M RITCHIE, Larry W OBERLEY and Joseph J CULLEN

Human gene therapy, Vol.15(3), pp.239-250

2004

DOI: 10.1089/104303404322886093

PMID: 15018733

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Abstract

Pancreatic cancer has low levels of antioxidant enzymes including manganese superoxide dismutase (MnSOD), which converts superoxide radical (O2.-) into hydrogen peroxide (H2O2), and glutathione peroxidase (GPx), which converts H2O2 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.

Biotechnology

Gene Therapy

Tumors

Liver. Biliary tract. Portal circulation. Exocrine pancreas

Transfusions. Complications. Transfusion reactions. Cell and gene therapy

Biological and medical sciences

Medical sciences

Fundamental and applied biological sciences. Psychology

Gastroenterology. Liver. Pancreas. Abdomen

Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy

Health. Pharmaceutical industry

Industrial applications and implications. Economical aspects

Applied cell therapy and gene therapy

Details

Title: Subtitle: Redox regulation of pancreatic cancer cell growth: Role of glutathione peroxidase in the suppression of the malignant phenotype
Creators: Jingru LIU - Department of Radiation Oncology, University of Iowa College of Medicine, Iowa City, IA 52242, United States
Marilyn M HINKHOUSE - Veterans Affairs Medical Center, Iowa City, IA 52242, United States
Wenqing Sun - Department of Radiation Oncology, University of Iowa College of Medicine, Iowa City, IA 52242, United States
Christine J WEYDERT - Department of Radiation Oncology, University of Iowa College of Medicine, Iowa City, IA 52242, United States
Justine M RITCHIE - Holden Comprehensive Cancer Center, University of Iowa College of Medicine, Iowa City, IA 52242, United States
Larry W OBERLEY - Department of Radiation Oncology, University of Iowa College of Medicine, Iowa City, IA 52242, United States
Joseph J CULLEN - Veterans Affairs Medical Center, Iowa City, IA 52242, United States
Resource Type: Journal article
Publication Details: Human gene therapy, Vol.15(3), pp.239-250
Publisher: Liebert; Larchmont, NY
DOI: 10.1089/104303404322886093
PMID: 15018733
ISSN: 1043-0342
eISSN: 1557-7422
Language: English
Date published: 2004
Academic Unit: Surgery; Radiation Oncology
Record Identifier: 9984047795102771

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