Molecular Medicine Reports, 2015, 11(3):564-571.

Potential therapeutic mechanism of genistein in breast cancer involves inhibition of cell cycle regulation

Ling Zhang, Bo Yang, Ke Zhou, et al

Department of Radiotherapy, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P.R. China

Genistein can prevent tumorigenesis and reduce the incidence of diseases that are dependent upon estrogen. Previous research, however, has shown that genistein can also increase the risk of breast cancer. Thus, the aim of the present study was to investigate the mechanism underlying the effect of genistein in breast cancer and to determine whether genistein produces a therapeutic effect or promotes the development of breast cancer. Gene microarray data obtained from three samples treated with alcohol (control group), three samples treated with 3 µmol/l genistein and three samples treated with 10 µmol/l genistein for 48 h, were downloaded from the Gene Expression Omnibus database. Analysis of the differentially expressed genes (DEGs) and functional enrichment in the two genistein groups was performed. The interaction networks of the DEGs were constructed and the overlapping network was extracted. Finally, the functions and pathways of the DEGs in the overlapping network were enriched. In total, 224 DEGs coexisted in the two genistein groups, and the most significant function of these was the cell cycle. The number and the fold change of expression values of the DEGs in the 10 µmol/l genistein group were significantly higher compared with that of the 3 µmol/l genistein group. The most significant function and pathway of the DEGs in the overlapping network was the cell cycle involving several genes, including GLIPR1, CDC20, BUB1, MCM2 and CCNB1. Thus, genistein stimulation resulted in gene expression changes in breast cancer cell lines and discrepancies increased with higher doses of genistein. The DEGs were most significantly associated with cell cycle regulation.

希腊《分子医学报告》，2015年3月

在乳腺癌中金雀异黄素抑制细胞周期调控的潜在治疗机理

张玲， 杨博，周科，等

中国四川成都，成都军区总医院放疗科

金雀异黄素可以预防肿瘤的发生并减少依赖雌激素疾病的发病率。然而，先前的研究表明，金雀异黄素还可以增加患乳腺癌的风险。因此，本研究的目的是探讨金雀异黄素对乳腺癌影响的机制，以确定金雀异黄素是否产生疗效，或促进乳腺癌的发展。用乙醇处理三种样品（对照组），用3µmol/L 金雀异黄素处理三种样品和用10µmol/L 金雀异黄素处理三种样品48 小时，从中得到基因微阵列数据，从基因表达的综合性数据库中下载。差异性表达基因 (DEGs) 的分析和实用的富集在两组金雀异黄素中进行。构造DEGs相互作用网络并且重叠部分被提取。最后，在重叠网络中D EGs的功能和途径增多。总之，在两种金雀异黄素组中一共有224 种DEGs并存，其中最重要的功能是细胞周期。DEGs表达值的数量和倍数的改变在10 µmol/L金雀异黄素组中显著高于与3 µmol/L 金雀异黄素组。在重叠网络中DEGs最重要的功能和通路是涉及几种基因的细胞周期，包括 GLIPR1、 CDC20、 BUB1、 MCM2 和 CCNB1。因此，金雀异黄素的刺激导致乳腺癌细胞中基因表达的变化并且更高剂量的金雀异黄素增强差异性。DEGs与细胞周期调控关系最明显。