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Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma

Cancer Gene Therapy volume 18, pages 250–259 (2011)Cite this article

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Abstract

Nuclear factor-kappa B (NF-κB) has a pivotal role in the progression and distant metastasis of cancers, including malignant bone tumors. To inhibit NF-κB activation, a new molecular therapy using synthetic double-stranded oligodeoxynucleotide (ODN) as a ‘decoy’ cis element against NF-κB has been developed. To determine whether pulmonary metastasis of osteosarcoma is reduced by inhibiting the action of NF-κB, NF-κB decoy ODN was transfected into the nuclei of murine osteosarcoma cells with high pulmonary metastatic potential, the LM8 cell line, using a three-dimensional alginate spheroid culture model. An in vitro study demonstrated the successful transfection of LM8 cells cultured in alginate beads by ‘naked’ NF-κB decoy ODN and that the activation of NF-κB signaling was significantly suppressed. Tumor growth was not affected by transfection of NF-κB decoy ODN, however, the expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) mRNA was markedly decreased. Furthermore, the transfection of ‘naked’ NF-κB decoy ODN effectively suppressed pulmonary metastasis in an in vivo alginate bead transplantation model. Our results suggest that NF-κB has a central and specific role in the regulation of tumor metastasis and could be a molecular target for development of anti-metastatic treatments for osteosarcoma.

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Acknowledgements

We thank Takahiro Iino and Kei Chiba for their technical assistance. This study was sponsored by grants from the Uehara Memorial Life Science Foundation and from the Ministry of Education, Culture, Sports, Science and Technology (Japan).

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Mie, Japan

    A Nishimura, K Akeda, T Matsubara, K Kusuzaki, A Matsumine, A Uchida & A Sudo

  2. Department of Orthopaedic Surgery, University of California, San Diego, CA, USA

    K Masuda

  3. AnGes MG, Osaka, Japan

    T Gemba

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Correspondence to K Akeda.

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Nishimura, A., Akeda, K., Matsubara, T. et al. Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma. Cancer Gene Ther 18, 250–259 (2011). https://doi.org/10.1038/cgt.2010.75

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