Chen Jun, Duan Yuxin, Zhang Xing, Ye Yu, Ge Bo, Chen Jian
Department of Histology and Embryology, Guilin Medical University, Guilin, 541004, China.
Food Funct. 2015 Mar;6(3):995-1000. doi: 10.1039/c4fo01141d.
Genistein is an estrogenic soy-derived compound belonging to the isoflavone class and shows anti-cancer effects. However, the specific cell apoptosis mechanisms of genistein have not been fully understood. In this study, we investigated the specific cell apoptosis mechanisms of genistein and the potential involvement of the IGF1R-Akt-Bcl-2 and Bax-mediated pathways in human breast cancer cells in vitro. MCF-7 human breast cancer cells were treated with various concentrations of genistein, and cell proliferation was evaluated by the MTT assay. Morphological changes in treated cells were examined by Hoechst 33258 staining, and treated cells were examined by flow cytometry. The levels of IGF-1R, p-Akt, Bcl-2, and Bax protein expression and Bcl-2 and Bax mRNA expression were evaluated by western blot and RT-PCR, respectively. Genistein inhibited the proliferation of MCF-7 cells and induced cell apoptosis, as determined by Hoechst staining and flow cytometry analysis. Furthermore, genistein induced the inactivation of IGF-1R and p-Akt and downregulated the Bcl-2/Bax protein ratio. These results suggest that genistein inhibited cell proliferation by inactivating the IGF-1R-PI3 K/Akt pathway and decreasing the Bcl-2/Bax mRNA and protein expressions. Our findings help elucidate the mechanisms by which genistein may contribute to the prevention of breast cancer carcinogenesis.
染料木黄酮是一种源自大豆的具有雌激素活性的化合物，属于异黄酮类，具有抗癌作用。然而，染料木黄酮具体的细胞凋亡机制尚未完全明确。在本研究中，我们在体外研究了染料木黄酮在人乳腺癌细胞中的具体细胞凋亡机制以及IGF1R-Akt-Bcl-2和Bax介导的信号通路的潜在作用。用不同浓度的染料木黄酮处理MCF-7人乳腺癌细胞，通过MTT法评估细胞增殖。用Hoechst 33258染色检测处理后细胞的形态变化，并用流式细胞术检测处理后的细胞。分别通过蛋白质免疫印迹法和逆转录-聚合酶链反应评估IGF-1R、p-Akt、Bcl-2和Bax蛋白表达水平以及Bcl-2和Bax mRNA表达水平。通过Hoechst染色和流式细胞术分析确定，染料木黄酮抑制MCF-7细胞的增殖并诱导细胞凋亡。此外，染料木黄酮诱导IGF-1R和p-Akt失活，并下调Bcl-2/Bax蛋白比例。这些结果表明，染料木黄酮通过使IGF-1R-PI3 K/Akt信号通路失活以及降低Bcl-2/Bax mRNA和蛋白表达来抑制细胞增殖。我们的研究结果有助于阐明染料木黄酮可能有助于预防乳腺癌发生的机制。
