J Cancer 2020; 11(19):5689-5699. doi:10.7150/jca.45970

Research Paper

Dihydromyricetin inhibits cell proliferation, migration, invasion and promotes apoptosis via regulating miR-21 in Human Cholangiocarcinoma Cells

Lei Chen1,2*, Zhou-Sheng Yang3*, Yang-Zhao Zhou4, Yang Deng5, Pei Jiang6✉, Sheng-Lan Tan1,2✉

1. Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China, 410011.
2. Institute of Clinical Pharmacy, Central South University, Changsha, China, 410011.
3. Department of Pharmacy, The People's Hopital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China, 530021.
4. Department of Cardiovascular 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 Clinical Pharmacy and Pharmacology, Jining First People's Hospital, Jining Medical University, Jining, China, 272000.
*These authors contributed equally in this paper.

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Citation:
Chen L, Yang ZS, Zhou YZ, Deng Y, Jiang P, Tan SL. Dihydromyricetin inhibits cell proliferation, migration, invasion and promotes apoptosis via regulating miR-21 in Human Cholangiocarcinoma Cells. J Cancer 2020; 11(19):5689-5699. doi:10.7150/jca.45970. Available from http://www.jcancer.org/v11p5689.htm

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Abstract

Dihydromyricetin, the most abundant natural flavonoid isolated from Ampelopsis grossedentata, exhibits broad anti-tumor effects. However, the effects of dihydromyricetin on cholangiocarcinoma remain unclear. This study examined the anti-tumor effects of dihydromyricetin in two human cholangiocarcinoma cell lines HCCC9810 and TFK-1, and the underlying mechanism was also investigated. Our study was the first to show that dihydromyricetin significantly inhibited cell proliferation, migration, invasion and promoted apoptosis in cholangiocarcinoma cells. By analyzing the TCGA dataset, we found that expression of miR-21, an oncogene and a potential target of anticancer drugs for cholangiocarcinoma, was upregulated in cholangiocarcinoma tissues compared to paired control tissues. Moreover, dihydromyricetin significantly reduced the expression of miR-21 in a dose-dependent manner. Overexpression of miR-21 remarkably abolished the inhibitory effects of dihydromyricetin on cell proliferation, migration, invasion and abrogated its effect of promoting cell apoptosis in both HCCC9810 and TFK-1 cells. Dihydromyricetin remarkably increased the expression of PTEN and decreased the expression of phosphorylated Akt, while overexpression of miR-21 abrogated the modulation of PTEN/ Akt pathway by dihydromyricetin. Taken together, our study demonstrates that dihydromyricetin inhibits cell proliferation, migration, invasion and promotes apoptosis in cholangiocarcinoma cells via regulating miR-21.

Keywords: Dihydromyricetin, cholangiocarcinoma, miR-21, PTEN, Akt