金雀异黄素通过Notch-1 途径抑制 NF-κB 活性来抑制 MDA-MB-231 三阴性乳腺癌细胞的生长_潘虹

针对病种：乳腺癌

发表时间：2012年8月

发表国家：希腊

登载刊物：国际分子医学杂志

研究单位：中国南京医科大学第一附属医院乳房手术科

研究人员：潘虹，周文斌，何伟，等

主要结论：我们的数据第一次表明，GEN通过以剂量依赖的方式在Nocth-1 信号转导通路上抑制 NF-κ B 活性，抑制MDA-MB-231 三阴乳腺癌细胞的生长。我们还发现，GEN下调了细胞周期蛋白 B1、 Bcl-2 和 Bcl-xl的表达，可能由 NF-κ B 的活性通过Notch-1 信号转导通路调节。总之，我们的研究结果表明通过Notch-1 通路抑制 NF-κ B的活性可能是GEN抑制三阴乳腺癌细胞生长的新机制。需要进一步的临床前和临床研究，来更深入地探讨GEN对治疗三阴性乳腺癌的应用.

International Journal of Molecular Medicine, 2012, 30(2):337-343(7).

Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth by inhibiting NF-κB activity via the Notch-1 pathway

Hong Pan, Wenbin Zhou, Wei He, et al

Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, P.R. China

Genistein (Gen) has been reported as a protective factor against breast cancer. However, the molecular mechanism by which Gen elicits its effects on triple-negative breast cancer cells has not been fully elucidated. In our study, the breast cancer cell line MDA-MB-231 was selected to determine the action of Gen on triple-negative breast cancer cells. MTT assay, flow cytometric analysis, siRNA transfection, western blotting and nuclear factor-κB (NF-κB) activation-nuclear translocation assay were used to address the role of NF-κB activity and the Notch-1 signaling pathway on the effects of Gen. Our study revealed that Gen elicited a dramatic effect on cell growth inhibition, in a dose-dependent and time-dependent manner. Treatment of MDA-MB-231 cells with 0, 5, 10 or 20 µM Gen induced apoptosis of 6.78, 18.98, 30.45 and 60.64%, respectively. Exposure of MDA-MB-231 cells to Gen also resulted in G2/M phase accumulation of cells corresponding to 4.93, 12.54, 18.93 and 30.95%, respectively. Furthermore, our data demonstrated for the first time that Gen inhibited the growth of MDA-MB-231 triple-negative breast cancer cells by inhibiting NF-κB activity via the Nocth-1 signaling pathway in a dose-dependent manner. We also found that Gen downregulated the expression of cyclin B1, Bcl-2 and Bcl-xL, possibly mediated by NF-κB activation via the Notch-1 signaling pathway. In conclusion, our results suggest that inhibition of NF-κB activity via the Notch-1 pathway may be a novel mechanism by which Gen suppresses the growth of triple-negative breast cancer cells. Further preclinical and clinical studies are warranted to further investigate the application of Gen for the treatment of triple-negative breast cancer.

希腊《国际分子医学杂志》，2012年8月

金雀异黄素通过Notch-1 途径抑制 NF-κ B 活性来抑制 MDA-MB-231 三阴性乳腺癌细胞的生长

潘虹，周文斌，何伟，等

中国南京医科大学第一附属医院乳房手术科

金雀异黄素（GEN）被报道可以作为预防乳腺癌的保护性因素。然而，其中GEN影响三阴乳腺癌细胞的分子机制尚未完全阐明。在我们的研究中，乳腺癌细胞 MDA-MB-231 被选定用来测试GEN对三阴乳腺癌细胞的作用。MTT、流式细胞术分析、 siRNA 转染、免疫印迹和核因子-κ B (NF-κ B) 激活核易位测定用于揭示GEN对 NF-κ B 活性和Notch-1 信号转导通路的影响作用。我们的研究显示GEN以剂量依赖性和时间依赖性的方式引起对细胞生长抑制的巨大影响。分别用0、 5、 10 或 20 µM GEN处理细胞 MDA-MB-231诱导6.78、 18.98、 30.45和 60.64%的凋亡。暴露于GEN的MDA-MB-231 细胞还会分别使4.93、 12.54、 18.93和 30.95%的细胞堆积在G2/M 期阶段。此外，我们的数据第一次表明，GEN通过以剂量依赖的方式在Nocth-1 信号转导通路上抑制 NF-κ B 活性，抑制MDA-MB-231 三阴乳腺癌细胞的生长。我们还发现，GEN下调了细胞周期蛋白 B1、 Bcl-2 和 Bcl-xl的表达，可能由 NF-κ B 的活性通过Notch-1 信号转导通路调节。总之，我们的研究结果表明通过Notch-1 通路抑制 NF-κ B的活性可能是GEN抑制三阴乳腺癌细胞生长的新机制。需要进一步的临床前和临床研究，来更深入地探讨GEN对治疗三阴性乳腺癌的应用。