Journal
JOURNAL OF CONTROLLED RELEASE
Volume 245, Issue -, Pages 1-14Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2016.11.024
Keywords
PDAC; VEGFRs; Triple-amiRNA; EMT
Funding
- Six Talent Peaks Project fund in Jiangsu, China [WSW-029]
- Technological Innovation and Demonstration of Social Undertakings Project fund of Nantong, Jiangsu, China [HS2014003]
- Translational Medicine Research fund from the Affiliated Hospital of Nantong University, Jiangsu, China [TDFzh2014011]
Ask authors/readers for more resources
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal outcome. Both novel prognostic markers and therapeutic targets are needed to improve the overall outcome of patients. Although single or double VEGFRs have been studied in PDAC, little is known about the role of triple combination of VEGFRs (VEGFR1, 2, and 3) in prognosis and therapy. We determined VEGFRs protein expression in 241 pancreatic tissues by tissue microarray immunohistochemistry (TMA-IHC), and correlated with patients' clinical characteristics and overall survival. Subsequently, we inactivated VEGFRs expression using artificial microRNAs (amiRNAs) in vitro. Triple combination of amiRNAs to VEGFRs reduced cell proliferation, increased apoptosis, and reduced cell migration and invasion in pancreatic cancer cell lines. In the mouse xenograft pancreatic cancer model, triple VEGFRs silencing significantly reduced tumor growth, had synergistic effect with standard chemotherapy, and was associated with inhibition of epithelial mesenchymal transition (EMT). We conclude that triple combination of VEGFRs is a prognostic marker for PDAC, and inhibition of VEGFRs expression via amiRNA represents a novel targeted therapy in PDAC through regulating EMT. (C) 2016 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available