(searched for: NF-κB Inhibition Suppresses Experimental Melanoma Lung Metastasis)
Published: 1 January 2020
Journal of Cancer Science and Clinical Therapeutics, Volume 4, pp 256-265; doi:10.26502/jcsct.5079070
Background: Although novel therapeutic regimens for melanoma continue to emerge, the best current clinical response rate is still less than 60%. Moreover, anti-melanoma 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. Methods and Results: 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 nm 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. Conclusion: Inhibition of melanoma NF-κB (p65) with systemically-delivered siRNA effectively impedes the growth and progression of experimental melanoma lung metastasis.
Phytotherapy Research, Volume 26, pp 568-578; doi:10.1002/ptr.3586
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