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. The proliferation and apoptosis of GBC-SD cells were detected by MTT assay and Annexin V/PI. The expressions of Mcl-1, Bcl-2 Bcl-xL, Bax, Bak, leaved-caspase 9, cleaved-caspase 3 and cleaved-PARP protein in GBC-SD cells after 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 test results showed that the apoptotic rate increased gradually with the increase of UMI-77 concentration in a dose-dependent manner. Western blotting 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 (P<0.05), but the expressions of Bcl-2 and Bcl-xL proteins had no statistical significance, and the expression levels of cleaved-caspase 9, cleaved-caspase 3 and cleaved-PARP proteins were significantly increased (P<0.05) after treatment with 10 μmol·L-1 UMI-77 for 24 h. Conclusion:Mcl-1 inhibitor UMI-77 can induce apoptosis of GBC-SD cells in a dose-dependent manner by caspase-mediated endogenous apoptosis pathway, therefore, Mcl-1 may become a new therapeutic target in the gallbladder cancer research.
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