Oncology Reports, 2014, 31(2):673-8.

Genistein attenuates cancer stem cell characteristics in gastric cancer through the downregulation of Gli1

Dayeon Yu, Hyun-Soo Shin, Yeo Song Lee, et al

Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Nephrology, Department of Internal Medicine, Ewha Womans University School of Medicine, Ewha Medical Research Center, Seoul, Republic of Korea

Genistein is an isoflavone from soy with multiple action targets in cellular processes. Hedgehog signaling and its activator Gli1 are involved not only in oncogenesis, but also in cancer stemness and overexpression of CD44, a typical cancer stem cell surface marker. It has been shown that levels of Gli1 and CD44 expression are downregulated by genistein. Genistein may modulate distinctive cellular characteristics in cancer stem cells by inhibiting Gli1-related signaling pathways. In the present study, we sorted cells from MKN45, a human gastric cancer cell line, according to CD44 expression. CD44(+) cells showed properties of cancer stem-like cells and formed sphere colonies. In addition, sonic hedgehog (Shh) signaling genes were upregulated in CD44(+) cells when compared with these levels in CD44(-) cells. When CD44(+) cancer stem-like cells were treated with genistein, Gli1 and CD44 mRNA and protein expression was significantly reduced. Moreover, other stem cell markers were downregulated by genistein. Gli1 siRNA was used to confirm the action of genistein in inhibiting Gli1 expression. The high cell migration capacity of CD44(+) cells was blocked by genistein. in conclusion, genistein inhibits Gli1 gene expression, resulting in the attenuation of cancer stem-like properties in gastric cancer cells. In addition, genistein suppresses the cell invasive capacity that is required for tumor growth and metastasis. Our data showed that genistein can be an effective agent for gastric cancer therapy by targeting cancer stem-like characteristics.

希腊《肿瘤学报告》，2014年2月

在胃癌中金雀异黄素通过下调 Gli1 抑制癌症干细胞的特性

柳多妍，申秀铉，李如松等

韩国首尔延世医科大学胃肠病学研究所内科医学部；梨花医学研究中心梨花女子大学医学院内科肾脏科

金雀异黄素是一种源自大豆的异黄酮，在细胞过程中有多个行动目标。Hedgehog信号及激活剂 Gli1 不仅参与癌变，而且参与了癌症干细胞和 CD44的过表达，是一种典型的癌症干细胞表面标记物。已证明金雀异黄素下调了Gli1 的水平和 CD44 的表达。金雀异黄素可能通过抑制 Gli1 相关的信号通路来调节肿瘤干细胞的特色。在本研究中，我们根据 CD44 表达将人体胃癌细胞MKN45分类。CD44(+) 细胞表现出癌症干细胞样细胞的属性，并形成球形菌落。此外，当与在 CD44(-) 细胞中的水平相比时在CD44(+) 细胞中音猬因子 (Shh) 信号转导基因被上调。当用金雀异黄素处理CD44(+) 癌症干细胞样细胞时，Gli1 和 CD44的 mRNA 及蛋白表达显著减少。此外，其他干细胞标志物被金雀异黄素下调。Gli1的 siRNA被用来确认金雀异黄素抑制 Gli1 表达的机理。金雀异黄素阻碍了 CD44(+) 细胞的高度迁移能力。总之，金雀异黄素抑制 Gli1 的基因表达，导致胃癌细胞的干细胞属性减弱。此外，金雀异黄素抑制了肿瘤生长和转移需要的细胞侵袭能力。我们的数据表明，金雀异黄素通过靶向肿瘤干细胞样特征可以作为治疗胃癌有效的药物。