title: Cyclodextrin mediated delivery of NF-κB and SRF siRNA reduces the invasion potential of prostate cancer cells in vitro.
abstract: 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.
authors.affiliation: Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: J C
authors.initials: JC
authors.lastname: Evans
authors.affiliation: Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: J
authors.initials: J
authors.lastname: McCarthy
authors.affiliation: Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
authors.forename: C
authors.initials: C
authors.lastname: Torres-Fuentes
authors.affiliation: Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
authors.forename: J F
authors.initials: JF
authors.lastname: Cryan
authors.affiliation: Centre for Synthesis and Chemical Biology, Conway Institute, University College Dublin, Dublin, Ireland.
authors.forename: J
authors.initials: J
authors.lastname: Ogier
authors.affiliation: Centre for Synthesis and Chemical Biology, Conway Institute, University College Dublin, Dublin, Ireland.
authors.forename: R
authors.initials: R
authors.lastname: Darcy
authors.affiliation: UCD Conway Institute of Biomolecular and Biomedical Research, UCD School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland.
authors.forename: R W
authors.initials: RW
authors.lastname: Watson
authors.affiliation: Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: C M
authors.initials: CM
authors.lastname: O'Driscoll
mesh_terms: D045744:Cell Line, Tumor; D003505:Cyclodextrins; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D026362:Serum Response Factor / Q000235:genetics*; D051996:Transcription Factor RelA / Q000235:genetics*
chemical_list: D003505:Cyclodextrins; D016328:NF-kappa B; C498143:RELA protein, human; D034741:RNA, Small Interfering; C476858:SRF protein, human; D026362:Serum Response Factor; D051996:Transcription Factor RelA