单羧酸转运蛋白1抑制剂AZD3965对胃癌BCG-823细胞增殖和凋亡的影响

目的:探究单羧酸转运蛋白1（MCT1）抑制剂AZD3965通过抑制肿瘤细胞MCT1对胃癌细胞BCG-823增殖及凋亡的影响及其相关的分子机制。方法:MTT法检测不同浓度AZD3965（0、20、40、80 μmol/L）对胃癌细胞的增殖抑制作用。通过倒置显微镜观察胃癌细胞BCG-823在不同浓度AZD3965（0、20、40、80 μmol/L）处理后细胞形态的改变。集落克隆形成实验观察AZD3965对胃癌细胞BCG-823集落形成能力的影响。PI单染流式细胞术检测AZD3965对胃癌细胞BCG-823细胞凋亡的影响。Western blotting检测AZD3965作用下MCT1和凋亡相关蛋白Bax、Bcl-2的表达。结果:经AZD3965作用后BCG-823细胞的生长受到抑制，且随着药物浓度和作用时间的增加，AZD3965对人胃癌细胞BCG-823的增殖抑制作用逐渐增强（P<0.01）。通过倒置显微镜观察不同浓度AZD3965（20、40、80 μmol/L）处理胃癌细胞后，相较空白对照组（0 μmol/L AZD3965）胃癌细胞数目明显减少，细胞发生皱缩破裂，细胞形态发生改变。集落克隆形成实验表明AZD3965对胃癌细胞BCG-823有增殖抑制作用。PI单染流式细胞术结果显示，20、40、80 μmol/L AZD3965处理BCG-823细胞24 h后，细胞的凋亡率分别为（13.33±4.13）%、（22.53±2.97）%和（36.63±5.23）%，与空白对照组（0 μmol/L AZD3965）相比明显升高（P<0.01）。Western blotting结果显示，AZD3965可以下调BCG-823细胞中MCT1、Bcl-2的表达和上调Bax的表达。结论:AZD3965可通过抑制MCT1活性，并且激活Bax和抑制Bcl-2，从而抑制胃癌细胞增殖和诱导细胞凋亡。

Effect of monocarboxylate transporter 1 inhibitor AZD3965 on the proliferation and apoptosis of gastric cancer BCG-823 cells

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.