Molecular disruption of NBS1 with targeted gene delivery enhances chemosensitisation in head and neck cancer.
Bottom Line: a fibroblast growth factor 2 (FGF2)-targeted adenoviral system can alter viral tropism and allow for improved transduction and reduced systemic toxicity.Finally, we estimated the distribution of adenoviral vector in the liver. the mutant NBS1 protein retains the binding ability and effectively suppresses the expression level of the MRN in infected cells.FGF2-targeted adenoviral system enhances the cisplatin chemosensitisation of mutant NBS1 and may avoid viral-associated liver toxicities.
Affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania School of Medicine, 415 Curie Boulevard, CRB Room 145, Philadelphia, PA 19104, USA.Show MeSH
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Mentions: To investigate the status and mechanism of an antiangiogenesis effect after FGF2-targeted Ad-NBS1 gene transfer in vitro, the expression levels of NF-κB proteins were analysed. NF-κB is a major factor in the Ras/Raf-1 angiogenesis pathway. The expression of NF-κB protein was significantly lower in FGF2-targeted Ad-NBS1-infected cells (0.37±0.03) when compared with uninfected control (0.53±0.04, P<0.01), Ad-GFP-infected (0.55±0.05, P<0.01), Ad-NBS1-infected (0.54±0.05, P<0.01) or FGF2-Ad-GFP-infected (0.53±0.02, P<0.01) cells (Figure 5). These results indicate that FGF2-targeted Ad-NBS1 may downregulate NF-κB activity and downregulation of NF-κB may result in antiangiogenesis in cancer cells.
Affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania School of Medicine, 415 Curie Boulevard, CRB Room 145, Philadelphia, PA 19104, USA.