Abstract:
Objective:To investigate the effect of monocarboxylate transporter 1(MCT1) inhibitor AZD3965 on the proliferation and apoptosis of gastric cancer BCG-823 cells,and explore its molecular mechanisms.
Methods:The inhibitory effects of different concentrations of AZD3965(0,20,40 and 80 μmol/L) on the proliferation of gastric cancer cells were detected using MTT assay.The morphology changes of the gastric cancer BCG-823 cells treated with different concentrations of AZD3965(0,20,40 and 80 μmol/L) were observed using inverted microscope.The effect of AZD3965 on the colony forming ability of gastric cancer BCG-823 cells was observed using colony formation assay.The effect of AZD3965 on the apoptosis of gastric cancer BCG-823 cells was detected by flow cytometry with PI staining.The expression levels of MCT1,Bax and Bcl-2 protein were detected using Western blotting after treatment with AZD3965.
Results:The cell proliferation of BCG-823 cells treated with AZD3965 was inhibited,and the inhibition effect of AZD3965 on the proliferation of BCG-823 cells significantly enhanced with the increasing of drug concentration and duration of action(
P<0.01).After treatment of gastric cancer cells with AZD3965(20,40 and 80 μmol/L),the number of gastric cancer cells significantly reduced,the cells collapsed and ruptured,and the cell morphology changed under inverted microscope compared with the control group.The colony formation assay showed that AZD3965 could inhibit the proliferation of gastric cancer BCG-823 cells.The results of PI staining showed that the apoptosis rates of BCG-823 cells treated with AZD3965(20,40 and 80 μmol/L) for 24 h were (13.33±4.13)%,(22.53±2.97)% and(36.63±5.23)%,respectively,and the apoptosis rate significantly increased compared with the control group(
P<0.01).Western blotting results showed that AZD3965 could down-regulate the expression levels of MCT1 and Bcl-2,and up-regulate the expression level of Bax in BCG-823 cells.
Conclusions:AZD3965 can inhibit the proliferation of gastric cancer cells,and induce apoptosis by inhibiting the MCT1 activity,activating Bax and inhibiting Bcl-2.