GSK-J4对人结肠癌细胞的增殖抑制作用

Inhibitory effect of human colon cancer cells by GSK-J4

目的:评价JMJD3抑制剂GSK-J4对人结肠癌细胞的抑制能力,并探讨其作用机制。方法:噻唑蓝比色(MTT)法测定癌细胞抑制率,克隆形成方法评价癌细胞的增殖能力,Transwell实验评价癌细胞的侵袭能力,流式细胞术分析癌细胞的凋亡和细胞周期状态,蛋白免疫印迹实验评价癌细胞内相关蛋白的表达水平。结果:GSK-J4对多种人结肠癌细胞的半抑制浓度IC_(50)为(0.71~4.57)μmol/L,能抑制癌细胞的增殖和侵袭,诱导细胞凋亡及S期细胞阻滞,上调癌细胞内H3K27位三甲基化水平,并且上调凋亡相关蛋白Cleaved Caspase-7、Cleaved PARP和细胞周期相关蛋白p27 Kip1的表达。结论:GSK-J4可以上调凋亡和细胞周期相关蛋白,促进癌细胞的内源性凋亡和S期阻滞,抑制多种人结肠癌细胞如HCT116、DLD-1的生长增殖和侵袭。

Objective:To evaluate the inhibitory effects of GSK-J4,a JMJD3 inhibitor,on human colon cancer cells,and explore the mechanism of the inhibitory effects.Methods:The cell inhibition rate was determined by phenytetrazoliumromide colorimetry(MTT)assay,and the proliferation capacity was evaluated through clone formation experiments.The invasive ability was evaluated using Transwell experiments,and analysis of apoptotic and cell cycles by flow cytometry.The expression levels of proteins were evaluated using immunoblot experiments.Results:The semi-inhibitory concentrations IC_(50)of GSK-J4 on human colon cancer cells were 0.71 to 4.57μmol/L.GSK-J4 inhibited proliferation and invasion,induced the apoptosis and S-phase cell block,furthermore up-regulated tri-methyl H3 K27 level,apoptosis-related protein Cleaved Caspase-7,Cleaved PARP and cell cycle associated protein p27 Kip1 in cancer cells.Conclusion:GSK-J4 can inhibit proliferation and invasion of human colon cancer cells,like HCT116 and DLD-1,by promoting endogenous apoptosis and S phase blocking,and up-regulating apoptosis and cell cycle-related protein.