Heparanase antisense oligodeoxynucleotide inhibits angiogenesis and metastasis of human mammary carcinoma cell xenografts in nude mice

ObjectiveTo evaluate the inhibitory effect of heparanase antisense oligodeoxynucleotide (AS-ODN) on the angiogenesis and metastasis of human mammary carcinoma cell xenografts in nude mice.MethodsThe AS-ODN complementary to the start codon region of heparanase mRNA and its control, scrambled nonsense oligodeoxynucleotide (NS-ODN) were designed and synthesized. A subcutaneous growth model and an acute hematogenous metastasis model of human mammary carcinoma were established in nude mice and were treated with ODNs. The heparanase expression in tumor was evaluated by RT-PCR and Western blot. The microvessel density (MVD) was measured by immunohistochemistry for factor VIII. The tumor volume was calculated and lung metastatic nodules were counted.ResultsThe heparanase expression, MVD, tumor volume and lung metastatic nodules in AS-ODN treated group were significantly decreased compared with that in NS-ODN treated group and that in PBS group (P<0. 01).ConclusionHeparanase AS-ODN has significant inhibitory effect on the angiogenesis and metastasis of human mammary carcinoma cell xenografts in nude mice.