Journal
CANCER BIOLOGY & THERAPY
Volume 17, Issue 4, Pages 449-456Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15384047.2016.1156257
Keywords
Gene targeted therapy; HBV; HCC; STAT3
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Funding
- Natural Science Foundation of China [81172789, 81373222]
- National Basic Research Program of China [2013CB531503]
- National Mega Project on Major Infectious Diseases Prevention and Treatment [2012ZX10002006]
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Hepatitis B virus (HBV) infection is a significant cause of liver disease pathogenesis, which results in the development of hepatic dysfunction, cirrhosis and hepatocellular carcinoma (HCC). Our previous studies showed that oncogene STAT3 might be an ideal target for HCC therapy. Here, we investigated whether targeting blockage of STAT3 signaling is efficient for HBV-related HCC. Based on the refractory of HCC and the persistence of HBV, in this study, we designed shRNAs targeting STAT3. The results showed that blocking STAT3 signaling by shRNAs could promote HBV positive HCC cell apoptosis and induce cell cycle arrest, resulting in HCC cell growth inhibition in vitro. Importantly, STAT3-shRNAs efficiently suppressed HBV replication, which would reduce HBV-derived stimulation to STAT3 signaling and augment STAT3-shRNAs-mediated anti-HCC effect. Finally, STAT3-shRNAs-mediated anti-HBV positive HCC effect was confirmed in xenograft nude mice. This study suggested that targeting STAT3 therapies such as STAT3-shRNAs may be an efficacious strategy for HBV-related HCC.
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