Inhibition Of N-desulfated Heparin On Metastasis In Rat With Walker-256 Transplanted Hepatoma

Objective In this study,we examined the effect of N-desulfated heparin on the expression of vascular endothelial growth factor (VEGF) and angiogenesis and metastasis and to assess their relevance to Walker-256 transplanted hepatoma.Methods Walker 256 carcinosarcoma was orthotopically transplanted into the liver of SD rats liver to establish the hepatoma model. Three days after treatment,mice were randomly divided into two groups which included normal saline gruop and N-desulfated heparin group. animals received either i.v. injections of normal saline or N-desulfated heparin(10mg/kg·d) twice weekly for three weeks. 21 days after operation all animals were sacrificed.Tisues from cancer and other organs was obtained for histopathological evaluation. Staining of factorⅧand VEGF was performed by immunohistochemistry method in routine paraffin-embeded sections.Results All of the animals (n=10) treated with normal saline developed metastatic tumors in the regional lymph nodes,liver and lung.Twelve of the animals (n=20) treated with N-desulfated heparin developed metastatic tumors in the organs examined(P﹤0.05).MVD was 80.90±15.30 in normal saline gruop and 66.85±17.11 in N-desulfated heparin group(t=2.192,P﹤0.05). The positive expression of VEGF was lower in N-desulfated heparin group(50%)than that in normal saline group(80%)(P﹤0.05).Conclusion Our findings indicate that N-desulfated heparin can inhibit the metastasis of liver cancer through inhibiting tumor VEGF expression, and tumor angiogenesis with no obvious anticoagulant activity.