title: Combination of Poly I:C and arsenic trioxide triggers apoptosis synergistically via activation of TLR3 and mitochondrial pathways in hepatocellular carcinoma cells.
abstract: Poly I:C (polyinosinic acid:polycytidylic acid), an analogue of dsRNA (double-stranded RNA), can lead to apoptosis in human cancer cells and has been used as an adjuvant to treat cancer patients. ATO (arsenic trioxide) is used effectively in the treatment of HCC (hepatocellular carcinoma). We sought to evaluate whether Poly I:C could enhance the potentiation of ATO in HCC. Combination of Poly I:C and ATO synergistically inhibited the growth of SMMC-7721 cells. Treatment with Poly I:C alone or combined with ATO-activated TLR3 (Toll-like receptor 3) pathway, increased ROS (reactive oxygen species) generation and mitochondrial dysfunction. The combined treatment also caused caspase-3, -8, -9 activation. Moreover, the combined therapy caused Bcl-2 and survivin down-regulation, Bax up-regulation and Bid activation. In conclusion, the Poly I:C and ATO combination is potentially a novel and effective approach for the treatment of HCC.
authors.affiliation: Clinical Immunology Department, Changshu Medical Testing Center, Changshu 215500, Peoples Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Shen
authors.forename: Tingwang
authors.initials: T
authors.lastname: Jiang
authors.forename: Huiqi
authors.initials: H
authors.lastname: Lu
authors.forename: Huanxing
authors.initials: H
authors.lastname: Han
authors.forename: Rongcheng
authors.initials: R
authors.lastname: Luo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000379:methods; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis / Q000235:genetics; D007369:Interferon Inducers / Q000494:pharmacology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D010087:Oxides / Q000494:pharmacology*; D011070:Poly I-C / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077022:Survivin; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D007369:Interferon Inducers; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D000077022:Survivin; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D011070:Poly I-C; D000077237:Arsenic Trioxide