Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma.
Cancer Gene Ther
; 18(4): 250-9, 2011 Apr.
Article
en En
| MEDLINE
| ID: mdl-21183950
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oligodesoxirribonucleótidos
/
Neoplasias Óseas
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Terapia Genética
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Osteosarcoma
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FN-kappa B
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Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cancer Gene Ther
Asunto de la revista:
GENETICA MEDICA
/
NEOPLASIAS
/
TERAPEUTICA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Reino Unido