Paeoniflorin Affects Hepatocellular Carcinoma Progression by Inhibiting Wnt/β-Catenin Pathway through Downregulation of 5-HT1D

Author(s): Yang Zhou, Xun Liu, Yahan Gao, Rulan Tan, Zhiyuan Wu, Qixin Zhong, Feng Zeng*

Journal Name: Current Pharmaceutical Biotechnology

Volume 22 , Issue 9 , 2021


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Graphical Abstract:


Abstract:

Background: Hepatocellular Carcinoma (HCC) is a primary liver cancer with high mortality. Paeoniflorin is a pinane monoterpene picroside with anti-tumor effect isolated from Chinese peony root and white peony root.

Objective: The study was conducted to investigate the underlying mechanism of Paeoniflorin (PF) regulating Hepatocellular Carcinoma (HCC) progression via 5-hydroxytryptamine receptor 1D (5-HT1D).

Methods: HepG2 and SMMC-7721 hepatoma cells were treated with different concentrations of PF (0, 5, 10, 20 μM). Cell proliferation, apoptosis, migration, and invasion were examined by CCK-8 and colony formation assays, flow cytometry, wound healing assay, and transwell assay, respectively. RTqPCR assay was used to detect the expression level of 5-HT1D, and Western blot assay was used to detect the expressions of 5-HT1D and Wnt/β-catenin pathway-related proteins.

Results: With the increase in PF concentration, the mRNA levels of 5-HT1D in HepG2 and SMMC- 7721 hepatoma cells were decreased in a dose-dependent manner, and the proliferation, colony formation, migration and invasion ability of cells were gradually weakened, while the apoptosis rate was gradually increased. Overexpression of 5-HT1D significantly promoted the proliferation, colony formation, migration and invasion of HepG2 and SMMC-7721 cells, and increased the expression of Wnt/β-catenin pathway-related proteins, β -actenin, survivin, C-myc, and Cyclin D1. Furthermore, 5-HT1D overexpression could reverse the effect of PF on hepatoma cells and inhibit the expressions of Wnt/β-catenin pathway-related proteins.

Conclusion: PF may inhibit the progression of HCC by blocking Wnt/β-catenin pathway expression through downregulating 5-HT1D.

Keywords: Hepatocellular carcinoma, paeoniflorin, 5-HT1D, Wnt/β-catenin pathway, proliferation, migration.

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Article Details

VOLUME: 22
ISSUE: 9
Year: 2021
Published on: 09 October, 2020
Page: [1246 - 1253]
Pages: 8
DOI: 10.2174/1389201021666201009153808
Price: $65

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