Angiogenesis in residual cancer and roles of HIF-1α, VEGF, and MMP-9 in the development of residual cancer after radiofrequency ablation and surgical resection in rabbits with liver cancer.

Abstract

The aim of the study was to investigate the changes of blood flow signal in residual cancer after ultrasound-guided radiofrequency ablation (RFA) treatment of rabbit liver cancer over time, and to analyse the correlation between changes in blood flow signal and changes in hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9) in residual cancer tissue after RFA. One hundred and ten rabbits were randomly selected, VX2 tumour cells were implanted subcutaneously, tumour cells were implanted in liver. Ninety rabbits were divided into three groups: Group 1 - untreated controls, Group 2 - RFA group, Group 3 - surgical resection group. Tumour size, blood flow signal, microvessel density (MVD) in liver cancer were assessed. Correlation of HIF-1a, VEGF, MMP-9 mRNA and protein expressions with blood flow signal in residual cancer were observed. Liver tumour was 2.3 ± 0.32 cm, significant differences in the grade of blood flow signal were noted among different time points (days 0, 3, 7, and 14; p < 0.05). Significant differences were also observed between the surgical resection and RFA groups at the same time points (p < 0.05). The MVD in the RFA group was lower than that in the control group, but higher than that in the surgical resection group. The immunohistochemical scores for VEGF and MMP-9 in the RFA group were lower than those in the control group, but higher than those in the surgical resection group. The grade of ultrasound blood flow signal was positively correlated with the expression of two angiogenesis-related factors, VEGF and MMP-9, and the MVD in the control, RFA, and surgical resection groups. There is a higher risk of tumour recurrence with RFA than with surgical resection.