Abstract: Objective: To investigate the effects of GSK2816126(GSK126), a specific inhibitor of zeste gene enhancer homolog 2 (EZH2), on the proliferation and apoptosis of lung adenocarcinoma A549 cells, and to elucidate their possible mechanisms. Methods: The A549 cells were cultured in vitro and divided into control group and different concentrations(1.0,2.5,5.0,10.0,15.0 μmol·L^-1)of GSK126 groups. MTT colorimetry was used to detect the survival rates of cells in various groups.Clone formation experiment was used to detect the number of colony formation and the colony formation rate was calculated. EdU imaging was used to detect the proliferation rates of cells in various groups. Hoechst-33342 fluorescence staining was used to observe the apoptotic morphology of cells in various groups; flow cytometry was used to detect the apoptotic rates of A549 cells in various groups. Western blotting method was used to detect the expression levels of protein kinase B (AKT), phosphorylated protein kinase B (p-AKT), B-cell lymphoma-2 proto oncogene (Bcl-2), Bcl-2 related X protein (Bax), aspartate specific cysteine proteinase-3 (caspase-3) and activated aspartate specific cysteine proteinase-3 (Cleaved-Caspase-3) proteins in the cells in various groups. Results: The MTT results showed that compared with control group, the survival rates of A549 cells in different concentrations of GSK126 groups were decreased with the increase of GSK126 concentration (P<0.05).The results of clone formation experiment showed that compared with control group, the number of colonies in different concentrations of GSK126 groups were decreased gradually with the increase of GSK126 concentration (P<0.05).The EdU imaging results showed that the proliferation rates of the cells in different concentrations of GSK126 groups were decreased significantly with the increase of GSK126 concentration compared with control group (P<0.01).The Hoechst-33342 staining and flow cytometry results showed that compared with control group, the apoptotic rates of the cells in different concentrations of GSK126 groups were increased significantly with the increase of GSK126 concentration (P<0.01).The Western blotting results showed that compared with control group, the expression levels of p-AKT and Bcl-2 proteins were decreased gradually with the increase of GSK126 concentration (P<0.05), and the expression levels of Bax and Cleaved-Caspase-3 proteins were increased gradually (P<0.05). Conclusion: GSK126 may inhibit the cell proliferation by reducing the phosphorylation level of AKT, and promote the apoptosis of lung cancer cells by inducing Bax/Bcl-2/Caspase-3 signal pathway activation and activating apoptosis pathway.

Key words: zeste gene enhancer homolog 2, lung neoplasms, GSK2816126, cell proliferation, apoptosis