Suppression of the malignant phenotype in pancreatic cancer by overexpression of phospholipid hydroperoxide glutathione peroxidase

Jingru Liu; Juan Du; Yuping Zhang; Wenqing Sun; Brian J Smith; Larry W Oberley; Joseph J Cullen

doi:10.1089/hum.2006.17.105

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Suppression of the malignant phenotype in pancreatic cancer by overexpression of phospholipid hydroperoxide glutathione peroxidase

Journal article

Peer reviewed

Suppression of the malignant phenotype in pancreatic cancer by overexpression of phospholipid hydroperoxide glutathione peroxidase

Jingru Liu, Juan Du, Yuping Zhang, Wenqing Sun, Brian J Smith, Larry W Oberley and Joseph J Cullen

Human gene therapy, Vol.17(1), pp.105-116

01/2006

DOI: 10.1089/hum.2006.17.105

PMID: 16409129

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Abstract

Phospholipid glutathione peroxidase (PhGPx) reduces lipid hydroperoxides generated in biomembranes and also uses a wide range of reducing cofactors in addition to glutathione. PhGPx is synthesized as a mitochondrial PhGPx form (L-form) and as a nonmitochondrial PhGPx form (S-form). Our aims were to determine whether overexpression of PhGPx altered pancreatic tumor cell behavior. Pancreatic cancer cell lines were found by Western blotting to have diminished levels of PhGPx-immunoreactive protein compared with normal human pancreas. To normalize the levels of this protein, PhGPx was overexpressed in MIA PaCa-2 and AsPC-1 human pancreatic cancer cells by infection with an adenovirus-PhGPx L-form construct (AdPhGPx- L-form) (0-200 MOI) or with an adenovirus-PhGPx S-form construct (AdPhGPx-S-form) (0-200 MOI), and cell growth, plating efficiency, and growth in soft agar were determined. Pancreatic cancer cells were also injected subcutaneously into nude mice and tumor volume was calculated. Single direct injections of the adenoviral- PhGPx constructs were made into preestablished tumors. In vitro, AdPhGPx-S-form demonstrated 80% tumor growth inhibition, whereas AdPhGPx-L-form demonstrated 95% tumor growth inhibition. Ad- PhGPx-L-form or AdPhGPx-S-form also decreased plating efficiency and growth in soft agar. AdPhGPx-Lform decreased in vivo tumor growth to a greater extent than did AdPhGPx-S-form. Because of the growthinhibitory effects of PhGPx, lipid hydroperoxides may play an important role in the growth of pancreatic cancer.

Neoplasm Transplantation

Glutathione Peroxidase - analysis

Humans

Neoplasms

Dose-Response Relationship, Drug

Cell Division

Adenoviridae - genetics

Female

Pancreas - enzymology

Cell Line

Gene Transfer Techniques

Glutathione Peroxidase - metabolism

Transduction, Genetic

Pancreatic Neoplasms - pathology

Pancreatic Neoplasms - enzymology

Pancreas - pathology

Linear Models

Glutathione Peroxidase - biosynthesis

Gene Expression Regulation, Enzymologic

Phenotype

Animals

Mice, Nude

Mice

Pancreas - growth & development

Pancreatic Neoplasms - therapy

Details

Title: Subtitle: Suppression of the malignant phenotype in pancreatic cancer by overexpression of phospholipid hydroperoxide glutathione peroxidase
Creators: Jingru Liu - Department of Radiation Oncology, University of Iowa College of Medicine, and Holden Comprehensive Cancer Center, Iowa City, IA 52242, USA
Juan Du
Yuping Zhang
Wenqing Sun
Brian J Smith
Larry W Oberley
Joseph J Cullen
Resource Type: Journal article
Publication Details: Human gene therapy, Vol.17(1), pp.105-116
Publisher: United States
DOI: 10.1089/hum.2006.17.105
PMID: 16409129
ISSN: 1043-0342
eISSN: 1557-7422
Grant note: CA 66081 / NCI NIH HHS DK 60618 / NIDDK NIH HHS
Language: English
Date published: 01/2006
Academic Unit: Biostatistics; Surgery; Radiation Oncology; Obstetrics and Gynecology; Holden Comprehensive Cancer Center
Record Identifier: 9983997363102771

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