Arsenic Trioxide and Promyelocytic Leukemia Protein-Adenovirus Synergistically Inhibit In Vitro and In Vivo Growth of a Hepatoma Cell Line

The present study investigated the in vitro and in vivo growth-inhibitory effects of combination therapy with arsenic trioxide (As 2 O 3 ) and an adenovirus expressing promyelocytic leukemia protein (Ad-PML). Growth of HepG2 cells in culture was not inhibited by As 2 O 3 at concentrations below 5 μmol/L (p > 0.05). However, growth was inhibited by Ad-PML alone and synergistic growth inhibition was observed following combined treatments (p 0.05), but were undetectable in the Ad-PML alone or Ad-PML plus As 2 O 3 groups. Finally, established HepG2 tumors in nude mice were injected with PBS, Ad-PML, As 2 O 3 , or Ad-PML plus As 2 O 3 , the tumor volumes were measured by ultrasound, and the therapeutic effects were compared. As 2 O 3 alone had no effect at concentrations below 5 μmol/L (p > 0.05), while Ad-PML alone at a multiplicity of infection of 20 or As 2 O 3 plus Ad-PML significantly decreased tumor volumes (p < 0.05). Thus, the combination of As 2 O 3 and Ad-PML has synergistic inhibitory effects on hepatocellular carcinoma (HCC), possibly resulting from regulation of apoptotic gene expression enhanced HCC apoptosis.