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.