Downregulation of survivin expression and elevation of caspase-3 activity involved in pitavastatin-induced HepG 2 cell apoptosis

Abstract

The aim of the present study was to research the apoptosis of human hepatocellular carcinoma cell line HepG 2 induced by pitavastatin. HepG 2 cells were treated with increasing doses of pitavastatin or with mevalonic acid for 48 h. The proliferation of cells was detected with WST-8. The morphology of the nucleus was observed under a microscope by Hoechst 33258 staining. The apoptosis peaks were examined by flow cytometry. The expression of survivin mRNA was examined with RT-PCR. The caspase-3 activity was detected with caspase-3 colorimetric protease assay. We found that growth inhibitory effects were observed for treatment with pitavastatin at 10-50 μM. Pitavastatin at 10 μM induced granular apoptotic bodies of HepG 2 cells. Furthermore, pitavastatin at 10 μM increased the appearance of sub-G1 population of HepG 2 cells. Finally, pitavastatin at 10 μM downregulated the expression of survivin mRNA and upregulated the caspase-3 activity, which was clearly related to the HMG-CoA reductase activity. These results suggest that pitavastatin at 10 μM induces apoptosis of HepG 2 cells, which is associated with the decreased expression of survivin mRNA and increased caspase-3 activity of HepG 2 cells.