zeste基因增强子同源物2抑制剂GSK126对舌鳞状细胞癌细胞增殖与凋亡的影响

Effect of enhancer of zeste homolog 2 inhibitor GSK126 on the proliferation and apoptosis of tongue squamous cell carcinoma

目的观察zeste基因增强子同源物2(EZH2)抑制剂GSK126对人舌鳞状细胞癌细胞体外增殖与凋亡的影响,并探讨其相关机制,为舌鳞状细胞癌的临床治疗提供新思路。方法将不同浓度的GSK126作用于舌鳞状细胞癌CAL-27细胞,通过甲基噻唑基四唑(MTT)、克隆形成、5-乙炔基-2’脱氧尿嘧啶核苷(EdU)荧光染色实验检测药物对细胞增殖能力的影响;采用Hoechst33342荧光染色、JC-1法观察细胞凋亡情况;采用Western blot法检测CAL-27细胞内相关蛋白细胞外调节蛋白激酶(ERK)、磷酸化的细胞外调节蛋白激酶(p-ERK)、Bax、Bcl-2、Cleaved caspase-9的表达水平。结果GSK126能抑制CAL-27细胞增殖并对细胞凋亡有促进作用。GSK126能下调细胞内p-ERK、Bcl-2的表达水平,同时可增加Bax、Cleaved caspase-9的表达(P<0.05)。结论GSK126可抑制舌鳞状细胞癌CAL-27细胞的增殖,并且能促进其凋亡,其机制可能与抑制MEK/ERK信号通路以及激活Bax/Bcl-2通路有关。

Objective This study aims to study the effect of the enhancer of zeste homolog 2(EZH2)inhibitor GSK126 on the proliferation and apoptosis of human tongue squamous cell carcinoma cells in vitro and explore its related mechanisms in order to obtain insights into the clinical treatment of tongue squamous cell carcinoma.Methods Different concentrations of GSK126 were applied to CAL-27 cells of tongue squamous cell carcinoma,and the effects of drugs on cell proliferation were detected through methyl thiazolyl tetrazolium(MTT)assay,colony formation assay,and 5-ethynyl-2’-deoxyuridine(EdU)fluorescence staining.Hoechst33342 fluorescence staining and the JC-1 method were used in observing apoptosis.The expression levels of extracellular regulated protein kinases(ERK),phospho-extracellular regulated protein kinases(p-ERK),Bax,Bcl-2,and Cleaved caspase-9 in Cal-27 cells were detected through Western blot.Results GSK126 inhibited CAL-27 cell proliferation and promoted apoptosis.GSK126 down-regulated the expression of p-ERK and Bcl-2 and increased the expression of Bax and Cleaved caspase-9(P<0.05).Conclusion GSK126 can inhibit the proliferation of CAL-27 cells in tongue squamous cell carcinoma and promote its apoptosis,and the related mechanism may be associated with the inhibition of the MEK/ERK signaling pathway and activation of the Bax/Bcl-2 pathway.