Dual specific antitumor effects of Semliki Forest virus-based DNA vector carrying suicide Escherichia coli purine nucleoside phosphorylase gene via Salmonella

  • Authors:
    • Zhi-Hao Chen
    • Ge-Ling Huang
    • Ya-Qin Tu
    • Yu Jiang
    • Wu-Xing Dai
  • View Affiliations

  • Published online on: April 16, 2013     https://doi.org/10.3892/ijo.2013.1900
  • Pages: 2009-2018
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The Escherichia coli purine nucleoside phospho­rylase/2-fluoro-2-deoxyadenosine (ePNP/F-dAdo) suicide system has demonstrated a powerful killing and bystander effects on tumor cells. However, several drawbacks to this approach remain to be resolved, such as the side-effects and the low efficiency of ePNP-targeted expression. A human telo-merase reverse transcriptase promoter-driven Semliki Forest virus-based DNA vector (pShT-ePNP) with high expression of the ePNP gene was constructed. Live attenuated Salmonella typhimurium 7207 (SL7207) was used initially as a vehicle to targetly transfer the large alphavirus vector into tumor cells. The in vitro quantitative analysis showed ~2-fold higher green fluorescent protein (GFP) expression for pShT-GFP than for conventional cytomegalovirus (CMV) promoter-mediated eukaryotic expression plasmids such as pIRES-GFP and the targeted expression of the ePNP gene in tumor cells was also detected by RT-PCR. After F-dAdo addition, the enzymatic conversion of F-Ado into 2-fluoroadmine (F-Ade) was tested by HPLC. Cell cytotoxicity assays showed that the significant inhibitory effect of the SL/pShT-ePNP system on tumor cells was dose- and time-dependent. Following oral administration, recombinant bacteria targetly allocated within the solid tumor and the expression of ePNP and GFP genes in vivo were detected by RT-PCR or observed by fluorescence microscopy. SL/pShT-ePNP and F-dAdo were also found to exert powerful therapeutic effects in combination against tumor growth and for prolonging the lifespan of tumor-bearing mice. These findings suggest that the SL/pShT-ePNP system may serve as a powerful strategy for tumor therapy.
View Figures
View References

Related Articles

Journal Cover

June 2013
Volume 42 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Chen Z, Huang G, Tu Y, Jiang Y and Dai W: Dual specific antitumor effects of Semliki Forest virus-based DNA vector carrying suicide Escherichia coli purine nucleoside phosphorylase gene via Salmonella. Int J Oncol 42: 2009-2018, 2013.
APA
Chen, Z., Huang, G., Tu, Y., Jiang, Y., & Dai, W. (2013). Dual specific antitumor effects of Semliki Forest virus-based DNA vector carrying suicide Escherichia coli purine nucleoside phosphorylase gene via Salmonella. International Journal of Oncology, 42, 2009-2018. https://doi.org/10.3892/ijo.2013.1900
MLA
Chen, Z., Huang, G., Tu, Y., Jiang, Y., Dai, W."Dual specific antitumor effects of Semliki Forest virus-based DNA vector carrying suicide Escherichia coli purine nucleoside phosphorylase gene via Salmonella". International Journal of Oncology 42.6 (2013): 2009-2018.
Chicago
Chen, Z., Huang, G., Tu, Y., Jiang, Y., Dai, W."Dual specific antitumor effects of Semliki Forest virus-based DNA vector carrying suicide Escherichia coli purine nucleoside phosphorylase gene via Salmonella". International Journal of Oncology 42, no. 6 (2013): 2009-2018. https://doi.org/10.3892/ijo.2013.1900