Effects of Rhein on Proliferation,Migration and Invasion of Hepatocellular Carcinoma Cells by Regulating Ras/ERK Signaling Pathway
Objective:To investigate the effects of rhein on the proliferation,migration and invasion of hepatocellular carcinoma(HCC)cells by regulating rat sarcoma protein(Ras)/extracellular signal-regulated kinase(ERK)signaling pathway.Methods:HepG2 cells were treated with different concentrations(0,12.50,25,50,100,150,200 mol/L)of rhein to detect cell activity and screen the best concentration of rhein.The cells were divided into control group,low,medium and high concentration rhein group,high concentration rhein+Ras/ERK activator group(high concentration rhein+ML-099 group),the number of cell colony formation,scratch healing rate,the number of cell invasion and the expression of Ras,p-ERK and ERK protein were detected in each group.Results:Rhein reduced the activity of HepG2 cells in a concentration-and time-dependent manner(P＜0.05),HepG2 cells were treated with 25,50,100 mol/L for 24 h for subsequent experiments.Compared with control group,the number of cell colony formation,the proportion of G0/G1 cells,cell scratch healing rate,the number of cell invasion and the expression of proto-oncogene(c-Myc),cyclin D1(CyclinDl),Ras and p-ERK/ERK protein in low,medium and high concentration groups of rhein decreased in a concentration-dependent manner,and the proportion of S phase and G2/M cells and the expression of p53 protein increased in a concentration-dependent manner(P＜0.05).Compared with rhein high concentration group,the number of cell colony formation,the proportion of G0/G1 cells,cell scratch healing rate,the number of cell invasion and the expression of c-Myc,CyclinD1,Ras and p-ERK/ERK protein in rhein hig concentration+ML-099 group were significantly increased,and the proportion of S phase and G2/M cells and the expressio of p53 protein were significantly decreased(P＜0.05).Conclusion:Rhein may inhibit the proliferation,migration and invasion of HCC cells by inhibiting the Ras/ERK signaling pathway.
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