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

Abstract

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 < .05), and the expressions of Bax and Bak proteins were significantly increased respectively (p < .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 < .05) in 24 h after GBC-SD cells were treated with 10 μmol/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.