1. SMAC-armed vaccinia virus induces both apoptosis and necroptosis and synergizes the efficiency of vinblastine in HCC.
- Author
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Pan Q, Huang Y, Chen L, Gu J, and Zhou X
- Subjects
- Apoptosis Regulatory Proteins, Carcinoma, Hepatocellular drug therapy, Cell Line, Tumor, Drug Synergism, Humans, Liver Neoplasms drug therapy, Necrosis, Thymidine Kinase genetics, Thymidine Kinase therapeutic use, Vinblastine therapeutic use, Antineoplastic Agents, Phytogenic pharmacology, Apoptosis drug effects, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular virology, Intracellular Signaling Peptides and Proteins, Liver Neoplasms pathology, Liver Neoplasms virology, Mitochondrial Proteins, Thymidine Kinase pharmacology, Vaccinia virus enzymology, Vaccinia virus genetics, Vinblastine pharmacology
- Abstract
Hepatocellular carcinoma (HCC) has particularly high incidence rate in Asia and its resistance to the chemotherapeutic drugs and cell death make it intractable. Vaccinia virus (VV) is a potential vehicle and has been widely used in cancer therapy. SMAC/DIABLO is a critical factor in activating caspases and eliminating inhibition of IAPs when the programmed cell death is promoted. In this study, we constructed a tumor-targeted vaccinia virus carrying SMAC/DIABLO gene that was knocked in the region of viral thymidine kinase gene (VV-SMAC). Our results showed that VV-SMAC efficiently infected and destroyed HCC cells via triggering both caspase-dependent apoptosis and necroptosis with depletion of IAPs. Furthermore, ripoptosome, a prerequisite complex of necroptosis, was assembled and induced by VV-SMAC. In addition, the combination of VV-SMAC and vinblastine represented a synergistic effect on HCC cells. In summary, our data suggest that VV-SMAC is a potential candidate and combination of VV-SMAC and vinblastine may provide a new avenue in treatment of HCC.
- Published
- 2014
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