染料木素抑制HER2阳性人乳腺癌与卵巢癌细胞增殖作用的研究

目的研究染料木素对人HER2高表达乳腺癌与卵巢癌细胞增殖的抑制作用,并探讨其作用机制。方法采用流式细胞分析技术、western blotting及细胞增殖与凋亡检测试剂盒等检测方法,对染料木素作用于HER2表达阴性的MCF-7细胞与通过稳定转染HER2而获得的MCF-7-1以及BT-474、SKOV-3等HER2阳性表达细胞的效果进行了剂量或时间反应关系的研究。结果浓度为0.1～10μg/ml的染料木素对HER2表达水平低的MCF-7细胞增殖的影响不大,而对HER2高表达的MCF-7-1、BT-474和SKOV-3细胞的增殖有显著的抑制作用(与DMSO对照组相比,P<0.01),且表现出剂量依赖性反应关系。用10μg/ml的染料木素作用12～48 h可以诱导BT-474细胞凋亡或坏死(与DMSO对照组相比,P<0.01),且表现出时间依赖性反应关系。结论染料木素能够明显抑制HER2阳性肿瘤细胞的增殖,这一作用可能是通过下调肿瘤细胞HER2信号转导而介导的。

The effect of genistein in inhibiting cell proliferation of human HER2-positive breast and ovarian cancer

Objective The inhibitive effects of genistein on the proliferation of human HER2-overexpressing breast and ovarian cancer cells were investigated, and the mechanism was explored. Methods Fluorescence-activated cell sorting （FACS） and western blotting methods, and cell proliferation assay kit from Promega and cell apoptosis as- say kit from Biolegend were used. The dose- or time-response relationship of genistein were observed on the HER2- negative breast cancer cell line MCF-7 or HER2-positive breast cancer cell lines BT474 and MCF-7-1 derived from MCF-7,and ovarian cancer cell line SKOV-3. Results The concentration of genistein ranged from 0.1-10 g/ml in the medium for 48 hours had a marked inhibition on the proliferation of HER2-positive tumor cell lines MCF-7-1, BT- 474 and SKOV-3, compared with DMSO control （ P 〈 0.01 ）, and a dose-dependent response was presented. However, genistein exerted a weak inhibitive effect on HER2-negative breast cancer cell line MCF-7. There was a significant apoptosis or necrosis effect of BT-474 cells induced by 10 g/ml genistein for 12-48 hours in comparision with DMSO control （ P 〈 0.01 ） , and a time-dependent response relationship. Moreover, genistein could downregulate HER2 receptor expression and AKT activity by analyzing its mechanism. Conclusion Genistein could efectively inhibit the proliferation of HER2-positive tumor cell lines, as should be through downregulating HER2 signalling.