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NF-κB Inhibition Suppresses Experimental Melanoma Lung Metastasis.

Authors
  • Stansel, Tomoko1
  • Wickline, Samuel A1
  • Pan, Hua1
  • 1 The USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Type
Published Article
Journal
Journal of cancer science and clinical therapeutics
Publication Date
Jan 01, 2020
Volume
4
Issue
3
Pages
256–265
Identifiers
DOI: 10.26502/jcsct.5079070
PMID: 32954352
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Although novel therapeutic regimens for melanoma continue to emerge, the best current clinical response rate is still less than 60%. Moreover, antimelanoma treatments contribute to toxicities in other vital organs. In this study, we elucidate the therapeutic advantages of siRNA targeting melanoma NF-κB canonical signaling pathway with a peptide-based gene delivery nanoplex system. In vitro treatment of melanoma B16-F10 cells was used to demonstrate delivery and efficacy of anti-NF-kB siRNA to cell cytoplasm with a 55 mn peptide-based gene delivery system. NF-κB (p65) knockdown was validated both at mRNA and protein levels by using RT2-PCR, western blot, and immunofluorescence cellular staining. Canonical p65 mRNA was reduced by 82% and p65 protein was reduced by 48%, which differed significantly from levels in control groups. In vivo treatment of a melanoma lung metastasis mouse model with 3-serial i.v. injections of p5RHH-p65 siRNA nanoparticles retarded growth of lung metastasis within one week by 76% (p=0.003) as compared to saline control treatments. Inhibition of melanoma NF-κB (p65) with systemically-delivered siRNA effectively impedes the growth and progression of experimental melanoma lung metastasis.

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