Genistein对乳腺癌异种移植瘤的抑制作用及其与uPA表达变化的关系

目的探讨三羟异黄酮(genistein)对原癌基因HER-2/neu高表达乳腺癌异种移植瘤的抑制作用及其与尿激酶型纤维蛋白溶酶原激活剂(urokinase type plasminogen activator, uPA)表达变化的关系.方法应用基因转染技术建立HER-2/neu高表达的乳腺癌MCF-7细胞(MCF-7/HER-2).BALB/c裸鼠皮下接种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细胞生长能力,应用Western blot 法观察移植瘤uPA的表达变化.结果 MCF-7/HER-2移植瘤与MCF-7移植瘤相比细胞增殖能力较强且uPA表达增加,而MCF-7/HER-2移植瘤经genistein和HER-2/neu抗体处理后,移植瘤细胞增殖能力减弱,其uPA表达降低.结论 Genistein能有效抑制HER-2/neu高表达乳腺癌异种移植瘤细胞的增殖能力,且这种作用与uPA的表达有关.

Inhibitory effect of genistein on HER-2/neu-overexpressing breast cancer xenograft tumors and its relationship with uPA expression

Objective To explore the inhibitory effect of genistein on oncogene HER-2/neu-overexpressing breast cancer xenograft tumors and its relationship with urokinase type plasminogen activator (uPA) expression. Methods HER-2/neu-overexpressing MCF-7 human breast cancer cells (MCF-7/HER-2) were generated by transfecting the HER-2/neu negative MCF-7 cells with HER-2/neu cDNA. MCF-7/HER-2 and MCF-7 xenograft models were established in BALB/c nude mice, and the nude mice with MCF-7/HER-2 xenograft were randomly divided into three groups: control group, genistein-treated group, and HER-2/neu antibody-treated group. The growth ability of xenograft tumors was analyzed by immunohistochemical staining with Ki-67 antibody, and uPA expression of xenograft tumors was analyzed by Western blotting. Results The growth ability and uPA expression were significantly higher in MCF-7/HER-2 xenograft tumors than those in MCF-7 xenograft tumors. MCF-7/HER-2 xenograft tumors treated by genistein or HER-2/neu antibody showed lower growth ability and uPA expression as compared with MCF-7/HER-2 xenograft tumors. Conclusion Genistein can inhibit the growth ability of HER-2/neu-overexpressing breast cancer xenograft tumors, which is associated with the uPA expression.