Dihydromyricetin Inhibits Tumor Growth and Epithelial-Mesenchymal Transition through regulating miR-455-3p in Cholangiocarcinoma

Cholangiocarcinoma (CCA) leads to poor prognosis due to high aggressiveness and common chemoresistance. Dihydromyricetin (DMY), the main bioactive compound isolated from Ampelopsis grossedentata, exhibits broad anti-tumor effects. This study aimed to investigate the inhibitory effect of DMY on CCA t...

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Bibliographic Details
Published in:Journal of Cancer 2021-01, Vol.12 (20), p.6058-6070
Main Authors: Li, Xin, Yang, Zhou-Sheng, Cai, Wen-Wu, Deng, Yang, Chen, Lei, Tan, Sheng-Lan
Format: Article
Language:English
Subjects:
Cancer therapies
Cell adhesion & migration
Cell culture
Cell growth
Chemotherapy
Cholangiocarcinoma
Medical prognosis
Metastasis
MicroRNAs
Research Paper
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Summary:Cholangiocarcinoma (CCA) leads to poor prognosis due to high aggressiveness and common chemoresistance. Dihydromyricetin (DMY), the main bioactive compound isolated from Ampelopsis grossedentata, exhibits broad anti-tumor effects. This study aimed to investigate the inhibitory effect of DMY on CCA tumor growth and epithelial-mesenchymal transition (EMT) and its underlying mechanism in CCA. DMY treatment significantly inhibited cell proliferation and EMT in CCA cell lines. The expression of ZEB1 and vimentin were down-regulated, while the level of E-cadherin was increased after DMY treatment. By analyzing the TCGA dataset, we found that miR-455 expression was significantly downregulated, while the level of ZEB1 was up-regulated in human CCA tumor tissues compared to normal samples. Mechanistic studies showed that ZEB1 was a direct target of miR-455-3p in CCA. Moreover, DMY treatment potently increased miR-455-3p expression and inhibited ZEB1 expression. Inhibition of miR-455-3p expression abolished DMY's inhibitory effects on tumor growth and EMT in both CCA cells and cell-engrafted nude mice. Finally, DMY significantly suppressed the expressions of p-PI3K and p-AKT, while silencing miR-455-3p remarkably abrogated the inhibitory effect. In conclusion, DMY suppresses tumor growth and EMT through regulating miR-455-3p in human cholangiocarcinoma, suggesting a potential option for CCA treatment.
ISSN:1837-9664
1837-9664
DOI:10.7150/jca.61311