ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2021; 12(20):6058-6070. doi:10.7150/jca.61311 This issue Cite
Research Paper
Dihydromyricetin Inhibits Tumor Growth and Epithelial-Mesenchymal Transition through regulating miR-455-3p in Cholangiocarcinoma
1. Department of Vascular Surgery, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China, 410011.
2. The Institute of Vascular Diseases, Central South University, Changsha, Hunan, China, 410011.
3. Department of Pharmacy, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China, 530021.
4. Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China, 410011.
5. Department of pharmacy, The Third Hospital of Changsha, Changsha, China, 410015.
6. Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China, 410011.
7. Institute of Clinical Pharmacy, Central South University, Changsha, China, 410011.
Abstract
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.
Keywords: Dihydromyricetin, cholangiocarcinoma, miR-455-3p, epithelial-mesenchymal transition
Citation styles
