Triple-amiRNA VEGFRs inhibition in pancreatic cancer improves the efficacy of chemotherapy through EMT regulation

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• 作者：Jianfei Huang^a ; ^b ; Haijun Mei^c ; Zhiyuan Tang^d ; Jieying Li^b ; Xiaojing Zhang^b ; Yixiang Lu^e ; Fang Huang^b ; Qin Jin^b ; Zhiwei Wang^c ; ^{wzw3639@126.com}
• 关键词：PDAC ; VEGFRs ; Triple-amiRNA ; EMT
• 刊名：Journal of Controlled Release
• 出版年：2017
• 出版时间：10 January 2017
• 年：2017
• 卷：245
• 期：Complete
• 页码：1-14
• 全文大小：2688 K
• 卷排序：245

文摘

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.