Nutrition & Cancer, 2010, 62(5):641-7.

Genistein induces growth inhibition and G2/M arrest in nasopharyngeal carcinoma cells

Hongyu Han, Caiyun Zhong, Xuchao Zhang, et al

Sun Yat-sen University, Guangzhou, Guangdong, P.R. China; University of California , Davis, California, USA, et al

Nasopharyngeal carcinoma (NPC) is an endemic malignant disease of the head and neck region with unique features including striking ethnic and geographic variations as well as multifactorial etiology. Previous studies have demonstrated the anticancer properties of genistein, the major soy isoflavonoid, in several human cancer cells such as breast, prostate, colon, gastric, lung, and hepatoma. However, the action of genistein in NPC cells has not been determined. In this study, we investigated the inhibitory effects of genistein on NPC cells and its possible underlying mechanisms. We found that genistein dose-dependently inhibited the proliferation of human NPC cell line CNE2 cells. DNA flow cytometric analysis revealed that 30 to 120 uM genistein induced dramatic G2/M phase arrest in NPC cells. The mRNA expression levels, as shown by gene expression array and quantitative real-time polymerase chain reaction, and the protein expression levels of the cell cycle regulators p21^Cip1 and ATR (Ataxia telangiectasia and Rad3 related) were elevated following genistein treatment. Interestingly, we also observed concomitant induction of p15^Ink4b in genistein induced inhibitory effects in NPC cells. Moreover, selective estrogen receptor modulators did not affect genistein induced growth inhibition. These findings provide new insights into the potential intervention of NPC with genistein.

美国《营养和癌症》2010年6月

金雀异黄素在鼻咽癌细胞中的抑制生长和 G2/M 期阻滞作用

韩宏宇，钟彩云，张旭超等

中国广东省广州市中山大学，美国加利福尼亚州加利福尼亚大学戴维斯分校等

鼻咽癌 (NPC) 是一种头颈部的地域性恶性疾病，具有罕见的特性，例如明显的种族和地理差异，以及多种多样的病因。以往的研究表明作为主要的大豆异黄酮，金雀异黄素对乳腺癌、 前列腺癌、 结肠癌、 胃癌、 肺癌和肝癌等几种肿瘤细胞均具有抗癌特性。然而，金雀异黄素对鼻咽癌细胞的作用机理尚未确定。在这篇论文中，我们探究了金雀异黄素对鼻咽癌细胞的抑制作用及其可能的基本机制。我们发现金雀异黄素抑制人类鼻咽癌细胞系 CNE2 细胞增殖呈剂量正相关。DNA 流式细胞术的分析揭示了从 30 到 120 uM的 金雀异黄素可以诱导鼻咽癌细胞发生突然的 G2/M 期阻滞。通过基因表达阵列和实时定量聚合酶链反应展示的mRNA 的表达水平和细胞周期调节剂p21^Cip1 以及ATR （共济失调毛细血管扩张症和相关Rad3） 的蛋白表达水平在经过染料木黄酮治疗后有所上升。有趣的是，我们还观察到在金雀异黄素诱导抑制鼻咽癌细胞的同时发生了p15^Ink4b的诱导。此外，选择性雌激素受体调节剂不会影响金雀异黄素发挥诱导生长抑制的作用。这些发现提供了金雀异黄素潜在干预鼻咽癌的新见解。