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BioMed Research International
Volume 2015 (2015), Article ID 382745, 12 pages
http://dx.doi.org/10.1155/2015/382745
Research Article

RNA-Based TWIST1 Inhibition via Dendrimer Complex to Reduce Breast Cancer Cell Metastasis

1Department of Neurosciences, City of Hope Beckman Research Institute, 1500 East Duarte Road, Duarte, CA 91010, USA
2Irell & Manella Graduate School of Biological Sciences, City of Hope Beckman Research Institute, 1500 East Duarte Road, Duarte, CA 91010, USA
3Division of Comparative Medicine, City of Hope Beckman Research Institute, 1500 East Duarte Road, Duarte, CA 91010, USA
4Department of Biological Sciences, California State University, Los Angeles, 5151 State University Drive, Los Angeles, CA 90032-8201, USA

Received 20 June 2014; Revised 31 December 2014; Accepted 31 December 2014

Academic Editor: Eric W.-F. Lam

Copyright © 2015 James Finlay et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Breast cancer is the leading cause of cancer-related deaths among women in the United States, and survival rates are lower for patients with metastases and/or triple-negative breast cancer (TNBC; ER, PR, and Her2 negative). Understanding the mechanisms of cancer metastasis is therefore crucial to identify new therapeutic targets and develop novel treatments to improve patient outcomes. A potential target is the TWIST1 transcription factor, which is often overexpressed in aggressive breast cancers and is a master regulator of cellular migration through epithelial-mesenchymal transition (EMT). Here, we demonstrate an siRNA-based TWIST1 silencing approach with delivery using a modified poly(amidoamine) (PAMAM) dendrimer. Our results demonstrate that SUM1315 TNBC cells efficiently take up PAMAM-siRNA complexes, leading to significant knockdown of TWIST1 and EMT-related target genes. Knockdown lasts up to one week after transfection and leads to a reduction in migration and invasion, as determined by wound healing and transwell assays. Furthermore, we demonstrate that PAMAM dendrimers can deliver siRNA to xenograft orthotopic tumors and siRNA remains in the tumor for at least four hours after treatment. These results suggest that further development of dendrimer-based delivery of siRNA for TWIST1 silencing may lead to a valuable adjunctive therapy for patients with TNBC.