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染料木黄酮通过上调胰腺癌细胞中 miR-34a 抑制细胞生长并诱导细胞凋亡。

Genistein inhibits cell growth and induces apoptosis through up-regulation of miR-34a in pancreatic cancer cells.

机构信息

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

出版信息

Curr Drug Targets. 2012 Dec;13(14):1750-6. doi: 10.2174/138945012804545597.

DOI:10.2174/138945012804545597
PMID:23140286
Abstract

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.

摘要

胰腺癌(PC)是美国癌症相关死亡的第四大常见原因,这表明需要设计新的治疗策略来改善被诊断为 PC 的患者的生存结果。最近,已经发现 microRNAs(miRNA)参与了肿瘤发生和发展的多个方面的调节,包括 PC。在这项研究中,我们研究了 miR-34a 是否在 PC 细胞的细胞生长和凋亡控制中发挥关键作用。我们发现 miR-34a 的重新表达(强制表达)抑制细胞生长并诱导细胞凋亡,同时下调 Notch-1 信号通路,这是 miR-34a 的一个靶标。此外,用天然化合物染料木黄酮处理 PC 细胞导致 miR-34a 的上调,导致 Notch-1 的下调,这与细胞生长的抑制和凋亡的诱导相关。我们的研究结果表明,染料木黄酮可以作为一种非毒性的 miRNA 激活剂,抑制 PC 细胞的增殖。

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