Current Drug Targets, 2012, 13(14):1750-6.

Genistein Inhibits Cell Growth and Induces Apoptosis Through Up-regulation of miR-34a in Pancreatic Cancer Cells

Jun Xia, Qiaoling Duan, Aamir Ahmad, et al

Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui, PR China, 233030

Pancreatic cancer (PC) is the fourth most common cause of cancer-related deaths in the United States, suggesting that designing novel therapeutic strategy is required to improve the survival outcome of patients diagnosed with PC. Recently, microRNAs (miRNA) have been found to be involved in the regulation of multiple aspects of tumor development and progression including PC. In this study, we investigate whether miR-34a plays a critical role in the control of cell growth and apoptosis in PC cells. We found that Re-expression (forced expression) of miR-34a inhibits cell growth and induces apoptosis, with concomitant down-regulation of Notch-1 signaling pathway, one of the target of miR-34a. Moreover, treatment of PC cells with a natural compound genistein led to the up-regulation of miR-34a, resulting in the down-regulation of Notch-1, which was correlated with inhibition of cell growth, and induction of apoptosis. Our findings suggest that genistein could function as a non-toxic activator of a miRNA that can suppress the proliferation of PC cells.

荷兰《当前药物靶点》，2012年12月

在胰腺癌细胞中金雀异黄素通过上调miR-34a抑制细胞生长并诱导细胞凋亡

夏军，段巧玲，阿米尔 艾哈迈德，等

中国安徽蚌埠医学院生物化学与分子生物学系

在美国胰腺癌 (PC) 是第四个最常见的与癌症相关的死亡原因，表明需要设计新的治疗策略提高 PC 患者的生存率。最近，microRNAs (miRNA) 已经被发现参与了PC肿瘤发生和进展多个方面的调控。在此研究中，我们探究了miR-34a 是否在控制PC细胞生长和凋亡方面发挥重要作用。我们发现miR-34a的再表达（强制表达）抑制了细胞的生长并诱导其凋亡，并下调相应的Notch-1信号转导通路，miR-34a 的目标之一。此外，用天然化合物金雀异黄素治疗PC 细胞使得miR-34a下调，导致Notch-1下调，与细胞生长抑制有关并诱导细胞凋亡。我们的研究结果表明，金雀异黄素可以作为无毒的miRNA活化剂来抑制PC细胞的增殖。