title: Polyinosinic-polycytidylic acid liposome induces human hepatoma cells apoptosis which correlates to the up-regulation of RIG-I like receptors.
abstract: Toll-like receptor 3 and RIG-I like receptors (RLRs; MDA5, RIG-I) are involved in cell growth inhibition and apoptosis. However, the toll-like receptor 3-related apoptotic pathway is insensitive to direct polyinosinic-polycytidylic acid (dsRNA analog) stimulation in hepatoma cells. To determine whether the strategy of transferring polyinosinic-polycytidylic acid into cells (polyinosinic-polycytidylic acid-liposome) could induce apoptosis in hepatoma cells through cytoplasm receptors, we examined the responses of innate immune receptors RLRs and toll-like receptor 3 in response to different stimulation. We found that the apoptosis could exclusively be detected under polyinosinic-polycytidylic acid-liposome stimulation, which involved the activation of the caspase pathway. Besides, the expression of RIG-I, MDA5, IFNbeta and interferon-stimulated gene 15 was increased significantly at an early stage. Moreover, the growth inhibition of polyinosinic-polycytidylic acid-liposome was confirmed in a mouse model. Taken together, these results suggest polyinosinic-polycytidylic acid-liposome could be used as a potential apoptotic agent in hepatocellular carcinoma cells and imply a potential therapeutic strategy.
authors.affiliation: Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Peng
authors.forename: Jianlin
authors.initials: J
authors.lastname: Geng
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D020169:Caspases / Q000187:drug effects; D045744:Cell Line, Tumor; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D007369:Interferon Inducers / Q000008:administration & dosage*; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta / Q000187:drug effects; D008081:Liposomes; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011070:Poly I-C / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D007369:Interferon Inducers; D008081:Liposomes; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D016899:Interferon-beta; D020169:Caspases; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D011070:Poly I-C