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

Objective:To evaluate the inhibitory effect of heparanase antisense oligodeoxynucleotide (AS-ODN) on the angiogenesis and metastasis of human mammary carcinoma cell xenografts in nude mice. Methods:The 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 estab- lished 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 factorⅧ.The tumor volume was calculated and lung metastatic nodules were counted.Results:The hep- aranase expression,MVD,tumor volume and lung metastatic nodules in AS-ODN treated group were sig- nificantly decreased compared with that in NS-ODN treated group and that in PBS group (P＜0.01).Con- clusion:Heparanase AS-ODN has significant inhibitory effect on the angiogenesis and metastasis of human mammary carcinoma cell xenografts in nude mice.