Polydatin regulates the proliferation,migration and cell cycle progression of gallbladder cancer cells by regulating the Akt/MDM2/p53 signaling pathway
Objective To investigate the effects of polydatin(PD)on the proliferation,migration and cell cycle progression of gallbladder cancer cells by regulating the protein kinase B(PKB/Akt)/oncogene MDM2/p53 tumor suppressor gene signaling pathway.Methods The human gallbladder cancer cell line GBC-SD was cultured in vitro,and treated with polydatin at the concentrations of 10-160mmol/L for 24 hours,48 hours and 72 hours.Cell proliferation was detected by CCK-8 assay to determine the optimal experimental concentration.GBC-SD cells were induced with blank control,low-dose,medium-dose and high-dose polydatin,and polydatin + Akt activator SC79.Cell migration was detected by Transwell assay.Apotpsis was detected by Hoechst staining.Flow cytometry was performed to detect apoptosis and cell cycle progression.Phosphorylation levels of Akt,MDM2 and p53 were detected by Western blot.A tumor-bearing mouse model was established to evaluate the effect of polydatin on the growth of gallbladder cancer.Results Treatment of polydatin at 10-160mmol/L for 24h significantly inhibited the proliferation of GBC-SD cells.We selected the concentrations of 10,20 and 40mmol/L as the low-dose,medium-dose and high-dose concentration.Compared with those of blank control,GBC-SD cells induced with low-dose,medium-dose and high-dose polydatin presented significantly lower migratory cell number,apoptotic rate,proportions of cells in G2/M and S phases and protein levels of p-Akt and p-MDM2,and significantly higher ratio of cells in G0/G1 phase and protein level of p-p53 in a dose-dependent manner(P<0.05).Compared with those induced with high-dose polydatin,GBC-SD cells induced with polydatin + SC79 presented significantly higher migratory cell number,apoptotic rate,proportions of cells in G2/M and S phases and protein levels of p-Akt and p-MDM2,and significantly lower ratio of cells in G0/G1 phase and protein level of p-p53(P<0.05).Treatment of polydatin significantly slowed down the growth of gallbladder cancer in mice(P<0.05).Conclusion Polydatin can block cell cycle and inhibit the proliferation and migration of gallbladder cancer cells by regulating the Akt/MDM2/p53 signaling pathway.
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