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Downregulation of TNF-α and VEGF expression by Sp1 decoy oligodeoxynucleotides in mouse melanoma tumor

Gene Therapy volume 10, pages 1992–1997 (2003)Cite this article

Abstract

Melanoma tumor growth and progression are highly dependent on adequate blood supply through angiogenesis. Since several genes involved in angiogenesis revealed potential binding sites for the transcription factor Sp1, we have examined the effects of local inoculation of Sp1 decoy oligodeoxynucleotides (ODNs) on the growth of transplanted murine melanoma tumors and the expression of VEGF and TNF-α within these tumors. Treatment with Sp1 decoy ODNs, but not their mutated form, led to a significant increase (P=0.041) of the tumor necrotic area, as evaluated morphometrically. Tumor necrosis was associated with a significant decrease of microvascular density (P=0.012) and relative vascular area (P=0.026), as determined by counting CD34-positive vascular structures within the tumor microenvironment of Sp1 decoy ODNs and control ODN-treated tumors. RT-PCR experiments showed a strong decrease in the levels of VEGF188 and VEGF164 isoforms and a moderate decrease of TNF-α in Sp1 decoy-treated tumors. Taken together, our results indicate that Sp1 decoy ODNs may inhibit angiogenesis by affecting the gene expression of key players in angiogenesis such as TNF-α and VEGF. These findings indicate that Sp1 decoy ODNs may be a potential new therapeutic tool in antiangiogenic therapy.

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Acknowledgements

Estela Maria Novak and Sérgio Paulo Bydlowski were supported by grants from FAPESP (Proc. #00/05381-2 and Proc. #00/09011-5), Martin Metzger from CAPES-DAAD and FAPESP (Proc. #99/00322-9), and Roger Chammas by FAPESP (Proc. #97/13100-9 and 98/14247-6).

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Authors and Affiliations

  1. Research and Molecular Biology Division, Pró-Sangue Hemocentro de São Paulo Foundation, São Paulo, Brazil

    E M Novak, K Dantas, C Manabe, J Pires, A C de Oliveira & S P Bydlowski

  2. Heart Institute, University of São Paulo School of Medicine, São Paulo, Brazil

    M Metzger

  3. Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São, Paulo, São Paulo, Brazil

    M Metzger

  4. Laboratório de Oncologia Experimental, Depto. de Radiologia, Faculdade de Medicina da Universidade de São Paulo, Brazil

    R Chammas & M da Costa

  5. Center for Research on Cell-based Therapy, Ribeirão Preto, Brazil

    R Chammas

  6. Department of Hematology, University of São Paulo School of Medicine, São Paulo, Brazil

    S P Bydlowski

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  1. E M Novak
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Correspondence to E M Novak.

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Novak, E., Metzger, M., Chammas, R. et al. Downregulation of TNF-α and VEGF expression by Sp1 decoy oligodeoxynucleotides in mouse melanoma tumor. Gene Ther 10, 1992–1997 (2003). https://doi.org/10.1038/sj.gt.3302111

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  • DOI: https://doi.org/10.1038/sj.gt.3302111

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