三羟异黄酮对乳腺癌异种移植瘤血管生成影响

目的 探讨三羟异黄酮(genlstein)对原癌基因(HER-2／neu)高表达乳腺癌血管形成的影响及其与血管内皮生长因子(VEGF)的关系。方法 应用基因转染技术建立HER—2／neu高表达的乳腺癌细胞(MCF—7／HER—2)。免疫缺陷裸鼠(BALB／c)皮下接种乳腺癌(MCF—7和MCF—7／HER—2)细胞，其中接种MCF—7／HER—2细胞的裸鼠随机分为3组：对照组；genistein处理组：HER—2／neu抗体处理组。应用免疫组化法观察移植瘤内微血管密度(microvessel density，MVD)和VEGF的表达变化。结果 MCF—7／HER—2移植瘤与MCF—7移植瘤相比血管密度较大。VEGF表达增强；MCF—7／HER—2移植瘤经genistein和HER—2／neu抗体处理后。移植瘤的血管密度减少，VEGF表达降低。结论 HER—2／neu高表达能促进乳腺癌的血管生成，genistein可能通过下调VEGF的表达从而抑制HER—2／neu高表达乳腺癌的血管生成。

Effect of genistein on angiogenesis in breast cancer xenograft tumor

Objective To explore the effect of genistein on angiogene sis in HER-2/neu-overexpressing breast cancer and the relationship with vascular endothelial growth factor.Methods HER-2/neu-overexpressing MCF-7 human breast cance r cells(MCF-7/HER-2) were generated by gene transfecting technique.MCF-7/HER-2 c ells and MCF-7 cells were injected into BALB/c nude mice.The nude mice with MCF- 7/HER-2 xenograft were randomly divided into three groups:control group,genistei n-treated group and HER-2/neu antibody-treated group.Microvessel density and VEG F expression exchang in xenograft tumors were analyzed with immunohistochemical staining.Results Microvessel density(MVD) and VEGF expression were significantly higher in MCF-7/HER-2 xenograft tumors than that in MCF-7 xenogra ft tumors.MCF-7/HER-2 xenograft tumors treated by genistein or HER-2/neu antibod y showed lower MVD and VEGF expression as compared with MCF-7/HER-2 xenograft tu mors.Conclusion The overexpression of HER-2/neu could promote angiogenesis in breast cancer,and genistein could inhibit angiogenesis in HER-2/ neu-overexpressing breast cancer through down-regulation expression of VEGF.