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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects*
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Arsenic Trioxide
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Arsenicals / pharmacology*
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BH3 Interacting Domain Death Agonist Protein / metabolism
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Carcinoma, Hepatocellular / drug therapy
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Carcinoma, Hepatocellular / metabolism*
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Caspase 3 / metabolism
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Caspase 8 / metabolism
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Caspase 9 / metabolism
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Cell Line, Tumor
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Cell Proliferation
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Drug Synergism
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Drug Therapy, Combination / methods
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Humans
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Inhibitor of Apoptosis Proteins / biosynthesis
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Inhibitor of Apoptosis Proteins / genetics
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Interferon Inducers / pharmacology
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Liver Neoplasms / drug therapy
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Liver Neoplasms / metabolism*
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Mitochondria / metabolism*
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Oxides / pharmacology*
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Poly I-C / pharmacology*
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Polymerase Chain Reaction
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Reactive Oxygen Species / metabolism
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Survivin
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Toll-Like Receptor 3 / metabolism*
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bcl-2-Associated X Protein / biosynthesis
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bcl-2-Associated X Protein / genetics
Substances
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Antineoplastic Agents
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Arsenicals
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BH3 Interacting Domain Death Agonist Protein
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BID protein, human
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BIRC5 protein, human
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Inhibitor of Apoptosis Proteins
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Interferon Inducers
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Oxides
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Proto-Oncogene Proteins c-bcl-2
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Reactive Oxygen Species
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Survivin
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TLR3 protein, human
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Toll-Like Receptor 3
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bcl-2-Associated X Protein
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Caspase 3
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Caspase 8
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Caspase 9
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Poly I-C
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Arsenic Trioxide