Potent antitumor activity of oncolytic adenovirus-mediated SOCS1 for hepatocellular carcinoma.
Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in diverse cancers, which contributes to the proliferation and survival of cancer cells by upregulating apoptosis inhibitors and cell cycle regulators. Suppressor of cytokine signaling 1 (SOCS1) is an important negative regulator of STAT pathways and is frequently silenced in many types of cancers. In this study, we used oncolytic adenoviral vector to deliver SOCS1 gene (AdCN305-SOCS1) to treat hepatocellular carcinoma (HCC). Our data showed that SOCS1 was downregulated in HCC cells by hypermethylation. AdCN305-SOCS1 was found selectively replicated, which led to SOCS1 overexpression in HCC cells. Infection of HCC cells with AdCN305-SOCS1 resulted in inhibition of STAT3 phosphorylation and downregulation of survivin, cyclin D1, Bcl-xL and C-myc. AdCN305-SOCS1 exhibited strong cytotoxicity to HCC cells by inducing apoptosis in vitro and in vivo. This study suggests that transfer of SOCS1 by an oncolytic adenovirus may be a potent antitumor approach for cancer therapy.
Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
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Liu
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Li
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Wei
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Cui
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Lou
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Wang
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Hu
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Qian
D000256:Adenoviridae / Q000235:genetics*; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000628:therapy*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004261:DNA Replication; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000628:therapy*; D050504:Oncolytic Viruses / Q000235:genetics*; D010766:Phosphorylation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism; D000077022:Survivin; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D016271:Proto-Oncogene Proteins c-myc; C108944:SOCS1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D000077022:Survivin; D051020:bcl-X Protein; D019938:Cyclin D1