Curcumin Combined with Chidamide Regulates Proliferation and Apoptosis of SKM-1 Cells by Suppressing AKT Phosphorylation and Upregulating p53 Expression
DENG Linli, WANG Li*
This study aimed to investigate the effect of curcumin combined with chidamide on SKM-1 cell proliferation and apoptosis and explore the underlying mechanism. SKM-1 cells were cultured in vitro, and the cells in the logarithmic growth phase were used for subsequent experiments. Cells in the control group were cultured routinely. Cells in the experimental groups were treated with different concentrations of curcumin (1, 5, 10, 20, 40 μmol/L), different concentrations of chidamide (0.5, 1, 2, 4, 8 μmol/L) and different concentrations of curcumin (5, 10 μmol/L) combined with different concentrations of chidamide (0.5, 1, 2, 4, 8 μmol/L), respectively. CCK-8 assay was used to detect the proliferation activity. CI (combination index) was calculated by Compusyn software. Cell cycle distribution and apoptosis were detected by flow cytometry. The protein expression levels of CDK2, p16, Caspase-3, AKT, p-AKT, p53 and γH2A.X in each group were detected by Western blot. The results showed that curcumin and chidamide inhibited the growth of SKM-1 cells in a time- and concentration-dependent manner. Curcumin (5 μmol/L) and chidamide (2 μmol/L) had a synergistic inhibitory effect on cell proliferation. The results of flow cytometry showed that 5 μmol/L curcumin combined with 2 μmol/L chidamide arrested the cell cycle at G0/G1 phase, and the apoptotic rate in the combination treatment group was significantly higher than that in the control and the single drug groups. The results of Western blot showed that compared with the control group, in the combination treatment group, the protein expression level of CDK2 and p-AKT/AKT ratio were significantly decreased while the protein expression levels of p16, caspase-3, p53 and γH2A.X were significantly increased. Collectively, curcumin combined with chidamide could significantly inhibit the proliferation of SKM-1 cells, block cell cycle and promote cell apoptosis, whose mechanism might be related to the inhibition of AKT phosphorylation and upregulation of p53 expression.
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