Yang Yang, Zang Aimin, Jia Youchao, Shang Yanhong, Zhang Zhuoqi, Ge Kun, Zhang Jinchao, Fan Wufang, Wang Bei
Department of Medical Oncology, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China.
College of Chemistry and Environmental Science, Key Laboratory of Chemical Biology of Hebei Province, Hebei University, Baoding, Hebei 071002, P.R. China.
Oncol Lett. 2016 Sep;12(3):2189-2193. doi: 10.3892/ol.2016.4817. Epub 2016 Jul 6.
Genistein is a soybean isoflavone; in its aglycone it has various biological activities. Animal experiments, clinical studies and epidemiological investigations suggest that genistein has preventative and curative functions for a number of diseases, particularly in cancer. The present study explored the potential anti-cancer effect of genistein by observing its role in inhibiting A549 human lung cancer cell proliferation and investigating the possible mechanism. A549 cells were exposed to various concentrations of genistein (0, 10, 25, 50, 100 and 200 µM; dissolved in physiological saline) for 1, 2 and 3 days. Subsequently, the viability of A549 cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell apoptosis was examined using a flow cytometer, caspase 3/9 activity was measured using commercial kits, reverse transcription quantitative polymerase chain reaction was used to analyze the miR-27a expression and western blotting was used to investigate MET protein expression. The results suggested a significant inhibition of A549 cell growth following treatment with genistein in a time- and dose-dependent manner. The current study also indicated that treatment with genistein significantly induces cell apoptosis and promotes caspase-3/9 activation of A549 cells in a dose-dependent manner. Further functional assays revealed that the anti-cancer effect of genistein activated microRNA-27a (miR-27a) expression levels and reduced MET protein expression in A549 cells. In conclusion, the present study demonstrates that genistein inhibits A549 human lung cancer cell proliferation. Furthermore, this study reports, for the first time, a correlation between the anti-cancer effect of genistein and miR-27a-mediated MET signaling.
染料木黄酮是一种大豆异黄酮;其苷元形式具有多种生物活性。动物实验、临床研究和流行病学调查表明,染料木黄酮对多种疾病具有预防和治疗作用,尤其是在癌症方面。本研究通过观察染料木黄酮在抑制A549人肺癌细胞增殖中的作用并探究其可能机制,探讨了染料木黄酮潜在的抗癌作用。将A549细胞暴露于不同浓度的染料木黄酮(0、10、25、50、100和200 μM;溶于生理盐水)中1、2和3天。随后,通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法测定A549细胞的活力,使用流式细胞仪检测细胞凋亡,使用商业试剂盒测量半胱天冬酶3/9活性,采用逆转录定量聚合酶链反应分析miR-27a表达,并用蛋白质免疫印迹法研究MET蛋白表达。结果表明,染料木黄酮处理后对A549细胞生长有显著抑制作用,且呈时间和剂量依赖性。本研究还表明,染料木黄酮处理以剂量依赖性方式显著诱导A549细胞凋亡并促进其半胱天冬酶-3/9激活。进一步的功能分析显示,染料木黄酮的抗癌作用激活了A549细胞中微小RNA-27a(miR-27a)的表达水平并降低了MET蛋白表达。总之,本研究表明染料木黄酮抑制A549人肺癌细胞增殖。此外,本研究首次报道了染料木黄酮的抗癌作用与miR-27a介导的MET信号传导之间的相关性。