Synergic effect of 3'-azido-3'-deoxythymidine and arsenic trioxide in suppressing hepatoma cells.

The aim of this study was to investigate the synergic antitumor effects of arsenic trioxide (As2O3) and 3'-azido-3'-deoxythymidine (AZT) on hepatoma cells and explore the possible molecular basis of these effects. These results showed that AZT enhanced the inhibitory effect of As2O3 on HepG2 and SMMC-7721 cell growth. The IC50 of As2O3 in combination with AZT was lower than that of As2O3 alone. A concentration-dependent synergic effect of As2O3 and AZT (CI < 1) was observed in all the tested combinations of these compounds. These results also showed that the combination of As2O3 and AZT dramatically and significantly increased the number of apoptotic cells in HepG2 and SMMC-7721 cells. Studies in vivo showed that the combination of As2O3 and AZT was statistically superior to either As2O3 or AZT alone in the treatment of tumor-bearing mice. As2O3 (1 mg/kg) containing AZT (50 mg/kg) inhibits proliferation of implanted hepatoma 22 by 56.35%. These results suggest that treating hepatoma with a combination of As2O3 and AZT offers the advantages of reduced toxic side effects and improved therapeutic efficacy. To understand the mechanism through which As2O3 and AZT suppress tumors, we studied the effects of these compounds, both separately, and in combination, on telomerase and caspase-3 activity. The results showed that the growth inhibitory and apoptotic effects of As2O3 and AZT on human hepatoma cells could be related to the inhibition of telomerase and the activation of caspase 3.