Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth by inhibiting NF-κB activity via the Notch-1 pathway
Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth by inhibiting NF-κB activity via the Notch-1 pathway
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DOI：
10.3892/ijmm.2012.990
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发表时间：
2012-08-01
影响因子：
5.4
通讯作者：
Wang, Shui
中科院分区：
文献类型：
--
作者：
Pan, Hong;Zhou, Wenbin;Wang, Shui
染料木黄酮（Gen）已被报道为预防乳腺癌的保护因子。然而，基因增强其对三阴性乳腺癌细胞作用的分子机制尚未完全阐明。在我们的研究中，选择乳腺癌细胞系MDA-MB-231来确定Gen对三阴性乳腺癌细胞的作用。采用MTT法、流式细胞术、siRNA转染、Western blotting和核因子-κ B（NF-κ B）活化-核转位法研究NF-κ B活性和Notch-1信号通路在Gen作用中的作用。用0、5、10和20 μ M Gen处理MDA-MB-231细胞，分别诱导6.78%、18.98%、30.45%和60.64%的凋亡。MDA-MB-231细胞暴露于Gen也导致G2/M期细胞蓄积，分别对应于4.93、12.54、18.93和30.95%。此外，我们的数据首次证明Gen通过Nocth-1信号通路以剂量依赖性方式抑制NF-κ B活性来抑制MDA-MB-231三阴性乳腺癌细胞的生长。我们还发现Gen下调了cyclin B1、Bcl-2和Bcl-xL的表达，这可能是通过Notch-1信号通路激活NF-κ B介导的。总之，我们的研究结果表明，通过Notch-1途径抑制NF-κ B活性可能是Gen抑制三阴性乳腺癌细胞生长的一种新机制。Gen在三阴性乳腺癌治疗中的应用有待于进一步的临床前和临床研究。
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-kappa B (NF-kappa B) activation-nuclear translocation assay were used to address the role of NF-kappa B 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 mu M 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-kappa B 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-kappa B activation via the Notch-1 signaling pathway. In conclusion, our results suggest that inhibition of NF-kappa B 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.