Intravenous injection of oligodeoxynucleotides to the nf-kappab binding site inhibits hepatic metastasis of m5076 reticulosarcoma in mice

ABSTRACT We have developed synthetic double-stranded oligodeoxynucleotides (ODN) as ‘decoy’ cis elements that block the binding of nuclear factors to promoter regions of targeted genes,

resulting in the inhibition of gene transactivation in vivo. In the present study, we employed decoy ODN targeting the transcription factor nuclear factor-kappaB (NF-kappaB) binding

cis-elements to hepatic metastasis of murine reticulosarcoma M5076 in mice. Intravenous inoculation of M5076 into mice caused a marked increase in gene expression of interleukin-1β, tumor

necrosis factor-α and intercellular adhesion molecule-1 in the liver, whereas intravenous treatment with NF-kappaB decoy ODN reduced M5076-induced transactivation of these genes. Treatment

with NF-kappaB decoy ODN, but not scrambled decoy ODN, significantly inhibited hepatic metastasis of M5076 in mice, and furthermore the combined treatment of NF-kappaB decoy ODN with an

anti-cancer drug resulted in complete inhibition of hepatic metastasis in half of the mice, without affecting myelosuppression induced by the anti-cancer drug. Here, NF-kappaB decoy ODN

inhibited hepatic metastasis of M5076 in mice possibly through a decrease in transactivation of important NF-kappaB-driven genes and also potentiated the anti-metastatic effect of an

anti-cancer drug, demonstrating the first successful in vivo therapy for cancer metastasis using NF-kappaB decoy ODN as a novel molecular decoy approach. Access through your institution Buy

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Kawamura and S Tsujimoto: The first two authors contributed equally to this work AUTHORS AND AFFILIATIONS * Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka,

Japan I Kawamura, S Tsujimoto, T Manda, M Tomoi & T Goto * Department of Geriatric Medicine, Osaka University Medical School, Japan R Morishita, N Tomita & T Ogihara * Division of

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 Google Scholar * T Manda View author publications You can also search for this author inPubMed Google Scholar * M Tomoi View author publications You can also search for this author inPubMed

 Google Scholar * N Tomita View author publications You can also search for this author inPubMed Google Scholar * T Goto View author publications You can also search for this author inPubMed

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inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kawamura, I., Morishita, R., Tsujimoto, S. _et al._ Intravenous injection of

oligodeoxynucleotides to the NF-kappaB binding site inhibits hepatic metastasis of M5076 reticulosarcoma in mice. _Gene Ther_ 8, 905–912 (2001). https://doi.org/10.1038/sj.gt.3301478

Download citation * Received: 17 August 2000 * Accepted: 06 April 2001 * Published: 27 June 2001 * Issue Date: 01 June 2001 * DOI: https://doi.org/10.1038/sj.gt.3301478 SHARE THIS ARTICLE

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by the Springer Nature SharedIt content-sharing initiative KEYWORDS * gene therapy * decoy * HVJ-liposome method * M5076 * hepatic metastasis