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

Abstract

Abstract. 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 µM 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.

Resistance to the mTOR inhibitor everolimus is reversed by the downregulation of survivin in breast cancer cells

“…Thus, it was speculated that forced negative control of the upregulation of survivin in MCF7 may restore the sensitivity of these cells to RAD001. YM155, an inhibitor of survivin, was selected, however, since YM155 has also been described as an inducer of apoptosis (13)(14)(15), we different concentrations of YM155 were tested on MCF7 cells in order to identify the concentration capable of inhibiting survivin expression without inducing immediate apoptosis. The concentration of 2.5 nM was selected for YM155 and used for the following experiments.…”

YM155 sensitizes HeLa cells to TRAIL‑mediated apoptosis via cFLIP and survivin downregulation

“…Small molecule inhibitor YM155, a survivin suppressor, inhibits cell proliferation and mediates apoptosis in breast ( 22 ), gastric ( 23 ), liver ( 24 ), and pancreatic ( 25 ) cancer models. Other than suppressing the levels of survivin in various types of cancer, YM155 has also been reported to have strong apoptogenic properties ( 26 , 27 ).…”