Inhibitory effect of genistein on the angiogenesis in HER-2/neu-overexpressing breast cancer xenograft in nude mice / 中国组织工程研究

ABSTRACT

BACKGROUND: Angiogenesis is an important prognostic indicator for malignant tumors. Breast cancer overexpressing oncogene HER-2/neu often denotes a poor prognosis. Many studies have demonstrated the antitumor effect of genistein against breast cancer.OBJECTIVE: To study the relationship between HER-2/neu expression and angiogenesis in breast cancer as well as the effect of genistein on the angiogenesis in HER-2/neu-overexpressing breast cancer.DESIGN: A randomized controlled observatory experiment with nude mice.SETTING: Department of nutrition and food hygiene of a military medical university.MATERIALS Twenty specific pathogen-free(SPF) normal female BALB/c nude mice weighing (10 ± 2) g, aged 3 to 4 weeks, were purchased from the Experimental Animal Center of the Third Military Medical University.METHODS: This study was carried out in the Department of Nutrition and Food Hygiene, Third Military Medical University from June 2001 to March 2002. HER-2/neu-overexpressing breast cancer cell line MCF-7/HER-2 was generated by transfecting MCF-7 cells with human HER-2/neu cDNA. MCF-7/HER-2 and MCF-7 cells were inoculated in female BALB/c nude mice to establish tumor-bearing mouse models. Four weeks after the inoculation, the mice with MCF-7/HER-2 xenografts were randomly divided into control,genistein treatment, and anti-HER-2/neu antibody treatment groups to receive corresponding treatments every other day for two weeks, at the end of which the tumor volume, microvessel density(MVD) and vascular endothelial growth factor(VEGF) expression in the xenografts were measured.MAIN OUTCOME MEASURES: MVD and VEGF expression in the xenograft tumor. Secondary outcome measures: Identification of HER-2/neu-transfected from MCF-7-transfected cells and the tumor volume.RESULTS: The MVD was 16 ±6, 98 ±21, 56± 18, and 52 ± 19 in each visual field in the MCF-7 xenografts group, control group, genstein treatment group and anti-HER-2/neu antibody treatment group recpectively. MVD and VEGF expression in MCF-7/HER-2 xenografts were higher than that in MCF-7 xenografts, and was reduced after treatment with genistein or anti-HER-2/neu antibody. The changes of tumor volume in these xenografts were consistent with the changes of MVD and VEGF.CONCLUSION: HER-2/neu overexpression in breast cancer promotes angiogenesis, and genistein can inhibit angiogenesis and growth of HER-2/neu-overexpressing breast cancer to improve the prognosis.