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

作者: J C Evans , J McCarthy , C Torres-Fuentes , J F Cryan , J Ogier

DOI: 10.1038/GT.2015.50

关键词: Prostate cancerBiologyViability assayCancer researchGene deliveryGene knockdownRNA interferenceCancerMetastasisGene silencingMolecular biology

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

参考文章(69)
Ravinder Mohan, Paul F. Schellhammer, Treatment Options for Localized Prostate Cancer American Family Physician. ,vol. 84, pp. 413- 420 ,(2011)
Laurie A. Shuman Moss, Sandra Jensen-Taubman, William G. Stetler-Stevenson, Matrix Metalloproteinases The American Journal of Pathology. ,vol. 181, pp. 1895- 1899 ,(2012) , 10.1016/J.AJPATH.2012.08.044
Gillian O'Hurley, Maria Prencipe, Dara Lundon, Amanda O'Neill, Susie Boyce, Anthony O'Grady, William M. Gallagher, Colm Morrissey, Elaine W. Kay, R. William G. Watson, The analysis of serum response factor expression in bone and soft tissue prostate cancer metastases The Prostate. ,vol. 74, pp. 306- 313 ,(2014) , 10.1002/PROS.22752
Andrew Fire, SiQun Xu, Mary K. Montgomery, Steven A. Kostas, Samuel E. Driver, Craig C. Mello, Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans Nature. ,vol. 391, pp. 806- 811 ,(1998) , 10.1038/35888
Alexander Hoffmann, David Baltimore, Circuitry of nuclear factor kappaB signaling. Immunological Reviews. ,vol. 210, pp. 171- 186 ,(2006) , 10.1111/J.0105-2896.2006.00375.X
A. M. O’Mahony, B. M. D. C. Godinho, J. Ogier, M. Devocelle, R. Darcy, J. F. Cryan, C. M. O’Driscoll, Click-Modified Cyclodextrins as Nonviral Vectors for Neuronal siRNA Delivery ACS Chemical Neuroscience. ,vol. 3, pp. 744- 752 ,(2012) , 10.1021/CN3000372
Jianfeng Guo, Julien R. Ogier, Stephane Desgranges, Raphael Darcy, Caitriona O′Driscoll, Anisamide-targeted cyclodextrin nanoparticles for siRNA delivery to prostate tumours in mice. Biomaterials. ,vol. 33, pp. 7775- 7784 ,(2012) , 10.1016/J.BIOMATERIALS.2012.07.012
Sanjeev Banerjee, Dejuan Kong, Asfar S. Azmi, Zhiwei Wang, Aamir Ahmad, Seema Sethi, Fazlul H. Sarkar, Restoring sensitivity to oxaliplatin by a novel approach in gemcitabine-resistant pancreatic cancer cells in vitro and in vivo. International Journal of Cancer. ,vol. 128, pp. 1240- 1250 ,(2011) , 10.1002/IJC.25658
Aoife M. O'Mahony, Julien Ogier, Stephane Desgranges, John F. Cryan, Raphael Darcy, Caitriona M. O'Driscoll, A click chemistry route to 2-functionalised PEGylated and cationic β-cyclodextrins: co-formulation opportunities for siRNA delivery. Organic and Biomolecular Chemistry. ,vol. 10, pp. 4954- 4960 ,(2012) , 10.1039/C2OB25490E
MANN-JEN HOUR, SHIH-CHANG TSAI, HSI-CHIN WU, MENG-WEI LIN, JING-GUNG CHUNG, JIN-BIN WU, JO-HUA CHIANG, MINORU TSUZUKI, JAI-SING YANG, Antitumor effects of the novel quinazolinone MJ-33: inhibition of metastasis through the MAPK, AKT, NF-κB and AP-1 signaling pathways in DU145 human prostate cancer cells. International Journal of Oncology. ,vol. 41, pp. 1513- 1519 ,(2012) , 10.3892/IJO.2012.1560