Thiostrepton Enhances The Inhibitory Effects Of Atra In Hepg2 Hepatocellular Carcinoma Cells

Aim: To investigate the effects of combination treatment of ATRA and thiostrepton on the HepG2 hepatocellular carcinoma cells and the underlying molecular mechanisms.Methods: MTT assay was used to analyze the viability of tumor cells.Flow cytometry was used to detect the apoptosis of tumor cells.Cell scratch assay was used to characterize the migration rate of tumor cells.Quantitative Real-time PCR assay was used to detect the mRNA expression levels of FOXM1 and its target genes CCNB1 and BIRC5.The protein expression levels of FOXM1 and its target gene CCNB1 was detected by Western Blot.Results: The MTT assay results showed that the viability of tumor cells in the group treated with the ATRA and thiostrepton combination was significantly lower than that in the group treated with either ATRA or thiostrepton.The apoptosis rate of cells detected by flow cytometry showed that the apoptosis rate of the combination treatment group was significantly higher than that of a single agent treatment group.The results of cell scratch experiment showed that the cell migration rate of the combination treatment group was lower than that of the single treatment group.Real-time fluorescence quantitative PCR data showed that the mRNA expression levels of FOXM1 and its target genes CCNB1 and BIRC5 in tumor cells of the combination treatment group were lower than those of a single agent treatment group.Western Blot results revealed that the protein expression levels of FOXM1 and its target genes CCNB1 in tumor cells of the combination treatment group were lower than those of a single agent treatment group.Conclusion: the combination of ATRA and thiostrepton has synergistic inhibitory effects on the proliferation and metastasis of HepG2 in hepatocellular carcinoma cells,and the molecular mechanism may be the synergistic inhibition of FOXM1 expression.