Abstract: Objective To study the changes in hypoxia-inducible factor (HIF1α, HIF2α) in the residual tumor cells in nude mice
bearing hepatocellular carcinoma (HCC) following treatment with high-intensity focused ultrasound (HIFU). Methods Thirty
nude mice bearing human HCC received treatment with HIFU. At 1, 3, and 5 days and 1 and 2 weeks after the treatment, the
mice were examined for pathological changes of the residual tumor with HE staining; SP immunohistochemistry, Western
blotting and real-time quantitative PCR were used to detect the protein and mRNA expressions of HIF1α and HIF2α in the
tumor. Results HE staining revealed the presence of residual tumor cells and large necrotic areas after the treatment.
Immunohistochemistry showed a gradual increment of HIF1α protein and mRNA expressions after the treatment, reaching the
peak level at 3 days (P<0.05) followed by progressive reduction at 5 days and 1 and 2 weeks. HIF2α expressions at either the
protein or mRNA levels exhibited no significant changes within 3 days after the treatment (P>0.05) but increased significantly
at 5 days and 1 and 2 weeks (P<0.05). Conclusion The changes of HIF1α and HIF2α in the residual tumor after HIFU treatment
in nude mice bearing HCC can be associated with tumor cell apoptosis and angiogenesis after the treatment.