Potent antitumor activity of oncolytic adenovirus-mediated SOCS1 for hepatocellular carcinoma

• DOI: 10.1038/gt.2012.4
• Publication Date: 2012-02-09T11:40:46Z
• Authors: L Liu; W Li; X Wei; Q Cui; W Lou; G Wang; X Hu; C Qian
• Keywords: DNA Replication; STAT3 Transcription Factor; 0303 health sciences; Carcinoma, Hepatocellular; Survivin; Genetic Vectors; Liver Neoplasms; Apoptosis; Suppressor of Cytokine Signaling Proteins; DNA Methylation; Adenoviridae; Inhibitor of Apoptosis Proteins; 3. Good health; Gene Expression Regulation, Neoplastic; Proto-Oncogene Proteins c-myc; Oncolytic Viruses; 03 medical and health sciences; HEK293 Cells; Suppressor of Cytokine Signaling 1 Protein; Cell Line, Tumor; Humans; Cyclin D1; Phosphorylation

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.