Home Neoplasma 2006 Neoplasma Vol.53, p.478-484, 2006

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Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

Published in English

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Neoplasma Vol.53, p.478-484, 2006

Title: Treatment of human tumor cells by combine gene therapy harnessing plasmids expressing human tumor necrosis factor alpha and bacterial cytosine deaminase suicide gene

Abstract: We have assessed the effect of combine cancer gene therapy with exogenous human tumor necrosis factor alpha (hTNF) and Escherichia coli cytosine deaminase (CD) suicide gene on two human breast adenocarcinoma cell lines MDA-MB-361 and SK-BR-3. Transfection of a plasmid containing hTNF under the control of a hybrid promoter resulted in expression of hTNF gene in vitro. Transduction of retroviral plasmid containing bacterial cytosine deaminase led to the expression of cytosine deaminase in adenocarcinoma cell lines as well. The significant increase in apoptotic cells and decrease of cell proliferation in both tumor cell lines was observed using combination treatment with hTNF expression plus CD/5-FC suicide system. Corresponding data were generated by MTT cell proliferation assay and by flow cytometric analysis. The presence of both genes after transduction of retroviral vector containing CD and transfection of hTNF plasmid was confirmed by PCR and RT-PCR. The additive cell killing effect due to the presence of bacterial CD and hTNF gene after activation of non-toxic prodrug was observed. Whether the bicistronic vector containing both therapeutic genes improve the therapy need to be assessed in the future.

Keywords: cancer gene therapy, retroviral vector, bacterial cytosine deaminase, tumor necrosis factor alpha, apoptosis
Year: 2006, Volume: 53, Issue: Page From: 478, Page To: 484

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