Enhanced antitumor activity of combined megestrol acetate and arsenic trioxide treatment in liver cancer cells.

Liver cancer is an aggressive malignancy with a very high fatality rate. Although megestrol acetate (MA) and arsenic trioxide (ATO) have shown an antitumor effect in liver cancer cells, the therapeutic benefits of MA or ATO alone in patients with liver cancer were limited. The aim of the present study was to elucidate whether the co-treatment of MA/ATO could enhance antitumor efficacy in liver cancer cell lines (Hep G2 and BEL 7402) and explore the underlying anti-cancer mechanisms. The cell viability, apoptotic response and expression levels of associated proteins were detected by Cell Counting Kit-8 assay, flow cytometry and western blotting, respectively. An xenograft model in nude mice bearing a Hep G2 tumor was used to estimate tumor growth in vivo. Co-treatment with MA/ATO markedly improved the inhibition of cell viability, enhanced apoptosis, and increased the phosphorylation of p38, c-Jun N-terminal kinase 1/2 and extracellular signal-regulated kinase 1/2 on liver cancer cell lines. Furthermore, the tumor growth in the murine Hep G2 cancer xenograft model was significantly inhibited by combined treatment with MA/ATO. The results indicated that MA/ATO combined treatment enhanced antitumor efficacy and possessed potential application for treating liver cancer.