title: VEGF-C ShRNA inhibits pancreatic cancer growth and lymphangiogenesis in an orthotopic fluorescent nude mouse model.
abstract: The aim of this study was to assess the inhibitory efficacy of short hairpin RNA (ShRNA) targeting vascular endothelial growth factor C (VEGF-C) in an orthotopic pancreatic cancer mouse model. BxPC-3 human pancreatic cancer cells expressing green fluorescent protein (GFP) were orthotopically implanted onto the pancreas of nude mice. All mice were randomly divided into four groups when the average tumor size had reached 100 mm(3) and were treated with either vehicle or gemcitabine at 150 mg/kg; or intravenous VEGF-C ShRNA at 150 mg/kg; or intratumoral VEGF-C ShRNA at 150 μg/kg. In vivo fluorescence imaging was performed to monitor tumor growth and metastasis during the study. Real-time quantitative polymerase chain reaction (RT-qPCR) and an enzyme-linked immunosorbent assay (ELISA) were performed to determine the mRNA and protein level of VEGF-C in tumor tissues. Lymphatic vessel marker D2-40, blood vessel marker CD31 and proliferation marker Ki67 expression of the tumor tissues were analyzed by immunohistochemistry staining. Intravenous and intratumoral VEGF-C ShRNA treatment significantly inhibited tumor growth, downregulated the expression of VEGF-C mRNA, reduced tumor microlymphatic vessel density (MLVD), and inhibited cancer cell proliferation. Gemcitabine, as the standard treatment for pancreatic cancer, demonstrated a stronger inhibitory effect on tumor growth, with less inhibition of MLVD and more inhibition of microvessel density (MVD) and proliferation than VEGF-C ShRNA. These results indicate that different mechanisms are associated with the efficacy of gemcitabine and VEGF-C ShRNA.
authors: Department of Radiology, East Hospital, Tongji University School of Medicine. 150 Jimo Road, Shanghai 200120, PR China.
authors: Yuzhen
authors: Y
authors: Shi
authors: Mingmin
authors: M
authors: Tong
authors: Yuefei
authors: Y
authors: Wu
authors: Zhijian
authors: Z
authors: Yang
authors: Robert M
authors: RM
authors: Hoffman
authors: Yong
authors: Y
authors: Zhang
authors: Ying
authors: Y
authors: Tian
authors: Mingmei
authors: M
authors: Qi
authors: Yanfei
authors: Y
authors: Lin
authors: Yongkang
authors: Y
authors: Liu
authors: Lingling
authors: L
authors: Dai
authors: Yu
authors: Y
authors: Sun
authors: Zhongqiu
authors: Z
authors: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D020868:Gene Silencing; D049452:Green Fluorescent Proteins; D006801:Humans; D007150:Immunohistochemistry; D042583:Lymphangiogenesis / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D034741:RNA, Small Interfering / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042582:Vascular Endothelial Growth Factor C / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D042582:Vascular Endothelial Growth Factor C; D003841:Deoxycytidine; D049452:Green Fluorescent Proteins; D000093542:Gemcitabine