title: Triple-amiRNA VEGFRs inhibition in pancreatic cancer improves the efficacy of chemotherapy through EMT regulation.
abstract: 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.
authors.affiliation: Department of Clinical Bio-bank, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China; Department of Pathology, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of General Surgery, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Mei
authors.affiliation: Department of Respiratory Medicine Laboratory, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Pathology, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China.
authors.forename: Jieying
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Maijie Biological Technology Co., Ltd. Nantong, Jiangsu 226007, China.
authors.forename: Yixiang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pathology, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Pathology, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Jin
authors.affiliation: Department of General Surgery, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China. Electronic address: wzw3639@126.com.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000008:administration & dosage* / Q000627:therapeutic use*; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics* / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D040262:Receptors, Vascular Endothelial Growth Factor; D002945:Cisplatin; D005472:Fluorouracil
keywords: EMT; PDAC; Triple-amiRNA; VEGFRs