A novel treatment strategy in hepatocellular carcinoma by down-regulation of histone deacetylase 1 expression using a shRNA lentiviral system.

Up to now, effective treatment methods for hepatocellular carcinoma (HCC), the fifth most prevalent cancer worldwide, have remained very limited. Previous studies have shown that histone deacetylase 1 (HDAC1) is highly expressed in HCC. The adoption of HDAC inhibitors in HCC treatment has also been studied, however, only moderate efficacy was observed. In the current study, using a clinically approved shRNA lentiviral system, we investigated whether the down-regulation of HDAC1 on mRNA level could suppress HCC progression. Our results showed that HDAC1 shRNA lentivirus infection could significantly reduce HCC Hep3B cell viability but have little impact on normal liver cell THLE-3. Cell cycle analysis revealed that HDAC1 shRNA lentivirus treatment could arrest HCC cells at G1 phase, which was probably achieved by modulating expression of cell cycle-related proteins including Cyclin D1, p21 and p27. Invasion assay showed that HDAC1 knock-down could dramatically reduce the invasiveness of HCC cells, which was correlated to the altered expression of some epithelial-mesenchymal transition related proteins including ZO-1, E-cadherin and Vimentin. Taken together, our findings have shown that down-regulation of HDAC1 on mRNA level using shRNA lentiviral system might be a novel alternative treatment strategy for HCC.