title: Double-stranded RNA-induced TLR3 activation inhibits angiogenesis and             triggers apoptosis of human hepatocellular carcinoma cells.
abstract: Toll-like receptor 3 (TLR3) is a member of the Toll-like receptors which             recognize pathogen-associated molecular patterns leading to the activation of             the innate immune response. Recent reports have strongly indicated that they play             important roles in cancer cells. Since TLR3 has been recently suggested as a possible             therapeutic target in certain types of cancers, in the present study, TLR3 expression             and its function were explored in hepatocellular carcinoma (HCC) and human umbilical             vein endothelial cells (HUVECs). The expression of TLR3 in various HCC cell lines             and HUVECs was detected using quantitative real-time PCR (qRT-PCR) and immunocytochemistry.             TLR3 activity was determined by Luciferase reporter assays. The effects of TLR3             double-stranded RNA (dsRNA) agonists on angiogenesis were tested by aortic ring             assay and HUVEC tube formation experiments. After dsRNA treatment, cell apoptosis             was assessed by Annexin V and PI staining through FACS, and the migration ability             was measured by a migration assay. The results showed that TLR3 was expressed             in HCC cell lines and HUVECs at the mRNA and protein level. Luciferase reporter             assays demonstrated that TLR3 was activated by the dsRNA analog BM-06 or poly(I:C).             Rat aortic ring outgrowth and endothelial cell tube formation were suppressed             after treatment with dsRNA. In addition, dsRNA triggered apoptosis in MHCC97H,             SMMC-7721 and HUVEC cell lines and inhibited cell migration. In conclusion, TLR3             agonists not only affect tumor microenvironment by suppressing angiogenesis but             also directly induce tumor cell apoptosis and inhibit tumor cell migration. TLR3             may be a new target for HCC therapy.
authors.affiliation: Department of Pathology, Nantong University School of Medicine, The Affiliated Tumor Hospital, Nantong 226001, PR China.
authors.forename: Zhongying
authors.initials: Z
authors.lastname: Guo
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yixin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Song
authors.initials: S
authors.lastname: He
authors.forename: Jin
authors.initials: J
authors.lastname: Qin
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Tang
authors.forename: Jiaming
authors.initials: J
authors.lastname: Zhou
authors.forename: Yingze
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008113:Liver Neoplasms / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D051381:Rats; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000378:metabolism*
chemical_list: D008024:Ligands; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D051196:Toll-Like Receptor 3