Silencing of survivin by YM155 induces apoptosis and growth arrest in hepatocellular carcinoma cells

Survivin overactivation is a frequent event in human hepatocellular carcinoma (HCC), due to its function in the induction of hepatocyte proliferation and apoptotic dysfunction. Recently, a novel survivin inhibitor named YM155, has demonstrated broad antitumor effects against various malignant tumors. Therefore, the present study aimed to explore how this agent may impact on HCC and elucidate its underlying mechanism of action. Immunohistochemical analysis was performed on 8 specimens of human HCC, to assess the protein expression of survivin and phosphorylated retinoblastoma tumor suppressor (p-Rb). In addition, in vitro, HepG2 and Huh7 human HCC cell lines were exposed to 100 mu M YM155 for up to 72 h and the cell viability was subsequently determined using MTT assay. Furthermore, the apoptotic status of YM155-treated HCC cells was investigated by flow cytometry, and the protein levels of survivin, procaspase-3 and p-Rb in YM155-treated HCC cells were assessed by immunoblotting analysis. The results demonstrated that HCC specimens expressed high levels of survivin and p-Rb protein compared with those of adjacent noncancerous liver tissues. In vitro, YM155 significantly induced HCC cell apoptosis and growth arrest. At the protein level, YM155 markedly inhibited survivin and p-Rb expression, and elevated procaspase-3. YM155 demonstrated significant antitumor effects on HCC cells in the present study. These effects were associated with its anti-proliferative and apoptosis-induction activities. YM155 requires further investigation as a novel agent for potential use as a therapeutic strategy for the treatment of HCC.