pVAX1 plasmid vector-mediated gene transfer of soluble TRAIL suppresses human hepatocellular carcinoma growth in nude mice

• Authors: Yan Zhang , Cun Hong Ma , Hua Liu , Xiu Mei Zhang , Wen Sheng Sun
• Languages of publication: EN

Abstracts

EN

The extracellular domain of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) may function as a soluble cytokine to selectively kill various cancer cells without toxicity to most normal cells. We used a high-biosafety plasmid pVAX1 as a vector and constructed a recombinant plasmid expressing the extracellular domain (95-281 aa) of human TRAIL fused with signal peptides of human IgGγ, designated as pVAX-sT. Transduction of human BEL7402 liver cancer cells with pVAX-sT led to high levels of sTRAIL protein in the cell culture media and induced apoptosis. The therapeutic potential of pVAX-sT was then evaluated in the BEL7402 transplanted naked mouse model. Subsequent intratumoral administration of naked pVAX-sT resulted in the expression of soluble TRAIL in the sera and the tumor site, as well as effective suppression of tumor growth, with no toxicity to liver. In conclusion, the successful inhibition of liver cancer growth and the absence of detectable toxicity suggest that pVAX-sT could be useful in the gene therapy of liver cancer.

Keywords

EN

pVAX1; soluble TRAIL; naked DNA; gene therapy; hepatocellular carcinoma

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2007
• Volume: 54
• Issue: 2
• Pages: 307-313

Dates

published

2007

received

2007-01-10

revised

2007-05-08

accepted

2007-05-22

(unknown)

2007-06-04

Contributors

author

Yan Zhang

• Institute of Pharmacology, Medical School of Shandong University, Jinan, China

author

Cun Hong Ma

• Institute of Immunology, Medical School of Shandong University, Jinan, China

author

Hua Liu

• Institute of Immunology, Medical School of Shandong University, Jinan, China

author

Xiu Mei Zhang

• Institute of Pharmacology, Medical School of Shandong University, Jinan, China

author

Wen Sheng Sun

• Institute of Immunology, Medical School of Shandong University, Jinan, China

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