Ginsenoside Rg3 inhibits renal cell carcinoma cell migration, invasion, colony formation, and tube formation and enhances apoptosis through promoting the DNA demethylation and histone acetylation
Zhiqiang Ma, Yan Zuo, Wei Wang
Abstract
OBJECTIVES: This study explored the effect and mechanism of Rg3 on renal cell carcinoma (RCC) progression. METHODS: RCC cells were treated with different concentrations of Rg3, 5-Aza-dc (a methyltransferase inhibitor) or TSA (a deacetylase inhibitor). Rg3-induced cytotoxicity, migration, invasion, colony formation, tube formation and apoptosis of RCC cells were evaluated by CCK-8, wound healing, Transwell, colony formation, tube formation and flow cytometry assays, respectively. Methylation and expressions of p53, p21 and p16, and expressions of methylation-related genes and histone deacetylases and histone acetylation-related genes (H3 (acetyl K14), H3 (acetyl K9), H4 (acetyl K12), H4 (acetyl K5) and H4 (acetyl K16)) were analysed by qRT-PCR and western blot. KEY FINDINGS: Rg3 dose-dependently decreased the viability, inhibited migration, invasion, colony formation and tube formation, and enhanced apoptosis of RCC cells. Rg3 enhanced the demethylation levels and expressions of p53, p21 and p16 as well as the expressions of histone acetylation-related genes, but repressed the expressions of methylation-related genes and histone deacetylases. Rg3 had the same effect as 5-Aza-dc and TSA did on the above-mentioned cellular changes. CONCLUSION: Rg3 restrains RCC cell migration, invasion, colony formation and tube formation, yet enhances apoptosis through promoting demethylation of p53, p21 and p16, and histone acetylation.