Mechanism of apoptosis induced by Mcl-1 inhibitor UMI-77 on gallbladder carcinoma GBC-SD cells

Objective:To investigate the mechanism of apoptosis induced by myeloid cell leukemia-1(Mcl-1)inhibitor UMI-77 on gallbladder carcinoma GBC-SD cells.Methods:GBC-SD cells were treated with different concentrations of UMI-77.GBC-SD cell proliferation and apoptosis were detected by MTT assay and Annexin V/PI.The expressions of Mcl-1,Bcl-2,Bcl-xL,Bax,Bak,cleaved-caspase 9,cleaved-caspase 3 and cleaved-PARP proteins in GBC-SD cells treated with UMI-77 were detected by Western blotting.Results:The results of MTT showed that different concentrations of UMI-77 had different inhibitory effects on cell proliferation of GBC-SD cells in a dose-dependent and time-dependent manner.Annexin V/PI results showed that the apoptosis rate was increasing gradually with the increase of UMI-77 concentration in a dose-dependent manner.Western blotting results showed that the expression of anti-apoptotic protein Mcl-1 was significantly decreased(p<0.05),and the expressions of Bax and Bak proteins were significantly increased respectively(p<0.05),but there were no significant changes in the expressions of Bcl-2 and Bcl-xL proteins,and the expression levels of cleaved-caspase 9,cleaved-caspase 3 and cleaved-PARP proteins were significantly increased(p<0.05)in 24 h after GBC-SD cells were treated with 10μmol/L of UMI-77.Conclusions:Mcl-1 inhibitor UMI-77 can induce the apoptosis of GBC-SD cells in a dose-dependent manner through the caspase-mediated endogenous apoptosis pathway.Therefore,Mcl-1 may become a new therapeutic target in the research on gallbladder cancer.