波形蛋白
上皮-间质转换
转移
癌症研究
基因敲除
下调和上调
肝细胞癌
体内
连环素
医学
鼻涕虫
钙粘蛋白
细胞培养
癌症
病理
生物
Wnt信号通路
内科学
细胞
信号转导
免疫组织化学
细胞生物学
生物化学
生物技术
基因
遗传学
作者
Wenqi Li,Shuhua Pei,Xiaojing Zhang,Defei Qi,Wenke Zhang,Yuanyuan Dou,Ruohan Yang,Xin Yao,Zhansheng Zhang,Songqiang Xie,Dong Fang,Hua Sun
标识
DOI:10.1016/j.ejphar.2022.174886
摘要
Hepatocellular carcinoma (HCC) is one of the malignant tumors with high incidence and mortality. The prognosis of HCC is poor due to the high postoperative recurrence rate and metastasis rate. Epithelial-mesenchymal transition (EMT) plays a key role in the metastasis of HCC, which is closely related to the invasion, intrahepatic metastasis and low survival rate. Here we demonstrated that cinobufotalin can upregulate epithelial markers (E-cadherin) and downregulate mesenchymal markers (N-cadherin, snail, slug and ZEB1) in HepG2, SMMC-7721 and SNU-368 cells. We further found that the mRNA and protein expression of β-catenin and its target genes (i.e. MMP7 and DKK1), which are related to tumor invasion and metastasis, were decreased after cinobufotalin treatment. Overexpression of β-catenin promoted EMT of HepG2 and SMMC-7721 cells, and cinobufotalin could antagonize this induction. While Knockdown of β-catenin could inhibit EMT and cinobufotalin enhanced this inhibition. In addition, cinobufotalin significantly suppressed the tumor EMT, as demonstrated by increased E-cadherin expression and decreased N-cadherin and vimentin expression, and inhibited formation and metastasis of lung metastases in vivo. In conclusion, our study has revealed a novel anticancer mechanism of cinobufotalin, which inhibits EMT progress by downregulating β-catenin, and then prevents the migration and invasion of HCC. These results provide convincing evidence for the development of cinobufotalin as a potential HCC metastasis inhibitor.
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