Abstract
The key to success with nonviral gene therapy as a treatment for cancer is to discover effective therapeutic genes and gene delivery methods and to understand how tumors are eradicated. We discovered that electroporation of IFN-α DNA into tumors in the SCCVII tumor-bearing mice led to tumor eradication in 50% of the mice and a more than two-fold increase in survival time when compared with controls (P = 0.0012). Analyses using cDNA array and Northern blot indicated that the genes responsible for the therapeutic effect of electro-IFN-α gene therapy included IRF-7, Granzyme A, Granzyme C, Gjb2, Krt14, Mig, IP-10 and MCP3. Because most of these genes have been known to either inhibit angiogenesis (Mig, IP-10), inhibit tumor growth (Gjb2, MCP3), kill tumor cells (Granzyme A and C), or induce expression of antitumor gene (IRF-7), they may become promising therapeutic gene candidates for a combination gene therapy approach to cancer treatment.
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Acknowledgements
The authors would like to thank Valentis, Inc., and Gentronics, Inc., for allowing us to use their gene constructs and electroporator, respectively, for this study. This work was partially supported by the Sam Walton Fund and a University of Arkansas for Medical Sciences pilot grant.
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Li, S., Xia, X., Zhang, X. et al. Regression of tumors by IFN-α electroporation gene therapy and analysis of the responsible genes by cDNA array. Gene Ther 9, 390–397 (2002). https://doi.org/10.1038/sj.gt.3301645
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DOI: https://doi.org/10.1038/sj.gt.3301645
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