Lack of mitochondrial DNA enhances growth of hepatocellular carcinoma in vitro and in vivo

To elucidate the role of mitochondrial DNA (mtDNA) in determination of growth of hepatocellular carcinoma, we examined wild-type Hepa1-6 cells and their ρ0 cells with depleted mtDNA in vitro and in vivo. Cultured ρ0 cells grew more rapidly than did wild-type cells. Production of reactive oxygen species (ROS) was higher in wild-type cells than in ρ0 cells. Hypoxia inhibited the growth of wild-type cells more markedly than that of ρ0 cells. Resistance to mitochondrial respiratory inhibitor-induced cell death was stronger in ρ0 cells than in wild-type cells. ρ0 cells subcutaneously inoculated in the hind thigh of mice grew more rapidly and formed larger solid tumors. These findings indicate that lack of mtDNA increases growth of hepatocellular carcinoma by decreasing ROS production and increasing resistance to mitochondrial respiratory inhibition.