Gu Yue, Xiao Linfeng, Ming Yanlin, Zheng Zhizhong, Li Wengang
Medical College of Xiamen University, Xiamen, Fujian, P.R. China.
The Research and Development Center for Medicine Plants and Plant Drugs, Xiamen Overseas Chinese Subtropical Plant Introduction Garden, Xiamen, Fujian, P.R. China.
Int J Oncol. 2016 May;48(5):1868-76. doi: 10.3892/ijo.2016.3413. Epub 2016 Mar 2.
Corilagin is a natural plant polyphenol tannic acid with antitumor, anti-inflammatory, and anti-oxidative properties. However, the mechanisms of its actions are largely unknown. Our group reported that corilagin could induce cell inhibition in human breast cancer cell line MCF-7 and human liver hepatocellular carcinoma cell lines HepG2. We report here that corilagin inhibits cholangiocarcinoma (CCA) development through regulating Notch signaling pathway. We found that, in vitro, corilagin inhibited CCA cell proliferation, migration and invasion, promoted CCA cell apoptosis, and inhibited Notch1 and Notch signaling pathway protein expression. Co-immunoprecipitation was used to establish Notch intracellular domain (NICD) interaction with MAML1 and P300 in CCA. Importantly, corilagin reduced Hes1 mRNA level through inhibiting Hes1 promoter activity. In nude mice, corilagin inhibited CCA growth and repressed the expression of Notch1 and mTOR. These results indicate that corilagin may control CCA cell growth by downregulating the expression of Notch1. Therefore, our findings suggest that corilagin may have the potential to become a new therapeutic drug for human CCA.
柯里拉京是一种具有抗肿瘤、抗炎和抗氧化特性的天然植物多酚单宁酸。然而，其作用机制在很大程度上尚不清楚。我们团队报道过柯里拉京可诱导人乳腺癌细胞系MCF-7和人肝癌细胞系HepG2发生细胞抑制。我们在此报告，柯里拉京通过调节Notch信号通路抑制胆管癌（CCA）的发展。我们发现，在体外，柯里拉京抑制CCA细胞增殖、迁移和侵袭，促进CCA细胞凋亡，并抑制Notch1和Notch信号通路蛋白表达。采用免疫共沉淀法在CCA中建立Notch细胞内结构域（NICD）与MAML1和P300的相互作用。重要的是，柯里拉京通过抑制Hes1启动子活性降低Hes1 mRNA水平。在裸鼠中，柯里拉京抑制CCA生长并抑制Notch1和mTOR的表达。这些结果表明，柯里拉京可能通过下调Notch1的表达来控制CCA细胞生长。因此，我们的研究结果表明，柯里拉京可能有潜力成为治疗人类CCA的新型治疗药物。
