Influence of transarterial chemoembolization on angiogenesis and expression of vascular endothelial growth factor and basic fibroblast growth factor in rat with Walker-256 transplanted hepatoma: an experimental study.

Abstract

After transarterial chemoembolization (TACE), the residual cancer cells are under extensive hypoxic or even anoxic environment. Hypoxia can lead to adaptive responses. For example, angiogenesis will help these cells survive. In this study, we examined the effect of TACE on angiogenesis and expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) and to assess their relevance to Walker-256 transplanted hepatoma. Male Wistar rats were inoculated with Walker-256 tumor in the left lobe of liver. Angiography and transarterial chemoembolization were performed at d14 after transplantation. Sixty rats bearing walker-256 transplanted hepatoma were randomly divided into control group, arterial infusion group and TACE group. Each group consisted of twenty rats. Normal saline, 5-Fu, 5-Fu and lipiodol were infused through hepatic artery respectively. Two weeks after the infusion, staining of factor VIII, VEGF and b-FGF was performed by immunohistochemistry method in routine paraffin-embedded sections. Microvessel density (MVD) was counted in endothelial cells with positive factor VIII. Their expression levels were analyzed in conjunction with the pathologic features. While a smaller tumor volume was found in TACE group (F=37.818, P<0.001), no statistical differences between MVD and expression of VEGF and b-FGF were found among the 3 groups. MVD of the control group, chemotherapy group and chemoemoblization group was 80.84+/-24.24, 83.05+/-20.29 and 85.20+/-23.91 (F=0.193, P=0.873), respectively. The positive expression of VEGF and b-FGF was 75%, 75%, 85% (chi2=0.449, P=0.799) and 30%, 25%, 30% (chi2=0.141, P=0.922), respectively. Statistical analysis revealed a positive correlation between the expression of VEGF and MVD (r=0.552, P<0.001). There has been little influence of lipiodol chemoembolization on the formation of tumor angiogenesis, but the development of neovascularization and expression of VEGF play important roles in establishment of collateral circulation and reconstruction of blood supply of residual cancer tissue.