Corilagin suppresses cholangiocarcinoma progression through Notch signaling pathway in vitro and in vivo.
Corilagin suppresses cholangiocarcinoma progression through Notch signaling pathway in vitro and in vivo.
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Corilagin 在体外和体内通过 Notch 信号通路抑制胆管癌进展
DOI：
10.3892/ijo.2016.3413
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发表时间：
2016-05
影响因子：
5.2
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Gu Y;Xiao L;Ming Y;Zheng Z;Li W
柯里拉京是一种天然植物多酚鞣酸，具有抗肿瘤、抗炎、抗氧化等作用。然而，其作用机制在很大程度上是未知的。本课题组研究了柯里拉京对人乳腺癌细胞株MCF-7和人肝癌细胞株HepG 2的抑制作用。我们在这里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，柯里拉京在体外抑制CCA细胞增殖、迁移和侵袭，促进CCA细胞凋亡，抑制Notch 1和Notch信号通路蛋白的表达。采用免疫共沉淀法建立Notch胞内结构域（NICD）与CCA中MAML 1和P300的相互作用。重要的是，柯里拉京通过抑制Hes 1启动子活性降低Hes 1 mRNA水平。在裸鼠中，柯里拉京抑制CCA生长并抑制Notch 1和mTOR的表达。这些结果表明柯里拉京可能通过下调Notch 1的表达来控制CCA细胞的生长。因此，我们的研究结果表明，柯里拉京可能有潜力成为一个新的治疗药物，人类CCA。
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.