在小细胞肺癌 H446 细胞中金雀异黄素通过下调 FoxM1表现出抗肿瘤作用_田甜甜 - 金转停_金雀异黄素Genistein

针对病种：肺癌

发表时间：2014年5月

发表国家：英国

登载刊物：肿瘤生物学

研究单位：中国山东省济南市山东大学齐鲁医院癌症中心药物肿瘤科和血液肿瘤科

研究人员：田甜甜，李继生，李蓓，等

主要结论：在这里，我们研究了金雀异黄素对小细胞肺癌 (SCLC) 细胞H446 的抗肿瘤作用以及基本分子机制。我们第一次证实，金雀异黄素施加给小细胞肺癌 H446 细胞的多重抗肿瘤效果至少部分是由 FoxM1 下调介导的。FoxM1 有潜力成为新型的治疗小细胞肺癌的药物，值得进一步研究.

Tumor Biology, 2014, 35(5):4137-45.

Genistein exhibits anti-cancer effects via down-regulating FoxM1 in H446 small-cell lung cancer cells

Tiantian Tian, Jisheng Li, Bei Li, et al

Department of Medical Oncology, Cancer center, Qilu Hospital of Shandong University, Jinan, China; Department of Hematology, Cancer Center, Qilu Hospital of Shandong University, Jinan, China

Genistein, a major isoflavone constituent in soybeans, has been reported to exhibit multiple anti-tumor effects, such as inducing cell cycle arrest, triggering apoptosis, and inactivating critical signaling pathways in a few human cancer cells. Here, we investigated the anti-tumor effects of genistein on the small-cell lung cancer (SCLC) cell line H446 and the underlying molecular mechanisms. H446 cells were treated with various concentrations of genistein, and experiments including CCK-8 assay, colony formation assay, flow cytometry analysis, wound healing assay, real-time polymerase chain reaction (PCR), western blot analysis, and plasmid transfection were used to investigate the influence of genistein on cell proliferation, migration ability, apoptosis, cell cycle progression, as well as the mRNA and protein alterations of FoxM1 pathway molecules. We found that genistein significantly inhibited the proliferation and migration ability of H446 cell, accompanied by apoptosis and G2/M phase cell cycle arrest. In addition, genistein enhanced the anti-proliferative effect of cisplatin on H446 cells. Importantly, genistein led to attenuation of the FoxM1 protein and down-regulated a series of FoxM1 target genes regulating cell cycle and apoptosis including Cdc25B, cyclin B1, and survivin. In addition, up-regulation of FoxM1 by cDNA transfection prior to genistein treatment could reduce genistein-induced H446 proliferation inhibition. Thus, for the first time, we demonstrated that genistein exerted multiple anti-tumor effects in H446 SCLC cell line at least partly mediated by the down-regulation of FoxM1. FoxM1 has the potential as a novel therapeutic agent in SCLC and is worthy of further study.

英国《肿瘤生物学》，2014年5月

在小细胞肺癌 H446 细胞中金雀异黄素通过下调 FoxM1表现出抗肿瘤作用

田甜甜，李继生，李蓓，等

中国山东省济南市山东大学齐鲁医院癌症中心药物肿瘤科和血液肿瘤科

金雀异黄素，一种大豆的主要异黄酮成分，已有报道显示出多种抗肿瘤作用，例如在一些人体肿瘤细胞中诱导细胞周期阻滞，触发凋亡，和关键肿瘤细胞信号转导的失活等。在这里，我们研究了金雀异黄素对小细胞肺癌 (SCLC) 细胞H446 的抗肿瘤作用以及基本分子机制。用不同浓度的金雀异黄素处理H446 细胞，实验包括 CCK-8 法、菌落形成法、流式细胞分析，创面愈合检测、实时聚合酶链反应 (PCR)、免疫印迹分析和质粒转染等试验被用来探究金雀异黄素对细胞增殖、迁移能力、细胞凋亡、细胞周期进程以及 FoxM1 通路分子 mRNA 和蛋白变化的影响。我们发现金雀异黄素明显抑制了 H446 细胞的增殖和迁移能力，伴有细胞凋亡和 G2/M 期细胞周期阻滞。此外，金雀异黄素增强了顺铂对 H446 细胞的抗增殖作用。重要的是，金雀异黄素减弱FoxM1 蛋白质并下调一系列 FoxM1 靶向基因调控的细胞周期和凋亡包括 Cdc25B，细胞周期蛋白 B1 和生存素。此外，在金雀异黄素治疗前由cDNA基因转染上调的 FoxM1，将能减弱金雀异黄素诱导的 H446 增殖抑制作用。因此，我们第一次证实，金雀异黄素施加给小细胞肺癌 H446 细胞的多重抗肿瘤效果至少部分是由 FoxM1 下调介导的。FoxM1 有潜力成为新型的治疗小细胞肺癌的药物，值得进一步研究。