Cyclodextrin mediated delivery of NF-κB and SRF siRNA reduces the invasion potential of prostate cancer cells in vitro

• Published in: Gene therapy Vol. 22; no. 10; pp. 802 - 810
• Main Authors: Evans, J C, McCarthy, J, Torres-Fuentes, C, Cryan, J F, Ogier, J, Darcy, R, Watson, R W, O’Driscoll, C M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-10-2015; Nature Publishing Group
• Subjects: 13/106; 13/109; 13/89; 38/77; 38/90; 631/154/152; 631/208/176/2016; 631/61/2300/1514; 631/61/2300/1851; 631/61/391/3932; 692/699/67/589/466; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Line, Tumor; Cell viability; Cyclodextrin; Cyclodextrins; Drug therapy; Gelatinase B; Gene Expression; Gene Therapy; Gene transfer; Genetic aspects; Genetic Vectors; Health aspects; Human Genetics; Humans; Inflammation; Male; Metastases; Metastasis; Nanotechnology; Neoplasm Invasiveness - genetics; NF-kappa B - genetics; NF-κB protein; original-article; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; RelA protein; Risk factors; RNA Interference; RNA, Small Interfering - administration & dosage; RNA, Small Interfering - genetics; RNA-mediated interference; Serum Response Factor - genetics; siRNA; Transcription Factor RelA - genetics; Ireland
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/gt.2015.50

Prostate cancer is the most common cancer in men of the western world. To date, no effective treatment exists for metastatic prostate cancer and consequently, there is an urgent need to develop new and improved therapeutics. In recent years, the therapeutic potential of RNA interference (RNAi) has been extensively explored in a wide range of diseases including prostate cancer using numerous gene delivery vectors. The aims of this study were to investigate the ability of a non-viral modified cyclodextrin (CD) vector to deliver siRNA to the highly metastatic PC-3 prostate cancer cell line, to quantify the resulting knockdown of the two target genes (
RelA
and
SRF
) and to study the effects of the silencing on metastasis. Data from a Matrigel
in vitro
invasion assay indicated that the silencing of the target genes achieved by the CD vector resulted in significant reductions (
P
=0.0001) in the metastatic potential of these cells. As the silencing of these target genes was shown not to have a negative impact on cell viability, we hypothesise that the mechanism of invasion inhibition is due, in part, to the significant reduction observed (
P⩽
0.0001) in the level of pro-inflammatory cytokine, MMP9, which is known to be implicated in the metastasis of prostate cancer.