目的:研究真核起始因子2α(eukaryotic initiation factor 2 alpha,eIF2α)的磷酸化对多柔比星诱导肝癌细胞凋亡的影响。方法:在采用eIF2α磷酸酶抑制剂salubrinal(抑制S51去磷酸化)和eIF2α突变载体eIF2αS51A(不能发生S51磷酸化)改变eIF2α磷酸化的基础上,利用流式细胞和免疫印迹技术分析eIF2α磷酸化对多柔比星诱导肝癌细胞LM3凋亡的影响。结果 :eIF2α突变载体eIF2αS51A抑制多柔比星介导的肝癌细胞LM3凋亡,而eIF2α磷酸酶抑制剂salubrinal则促进多柔比星介导的肝癌细胞LM3凋亡。结论:eIF2α的磷酸化在多柔比星介导的肝癌细胞凋亡中起重要作用。
Objective: To investigate the role of phosphorylation of eukaryotic initiation factor 2(eIF2)α in doxorubicin-induced apoptosis of human hepatocellular carcinoma cells.Methods: Dominant-negative mutant of eIF2α,eIF2αS51A and specific eIF2α phosphatase inhibitor,salubrinal were used to decrease and increase respectively the phosphorylation level of eIF2α in LM3 cells.Then the effect of the phosphorylation of eIF2 alpha on doxorubicin-induced LM3 cell apoptosis was analyzed by flow cytometry and Western blotting analysis.Results: eIF2αS51A pre-transfection obviously inhibited doxorubicin-mediated apoptosis in LM3 cells,while salubrinal pre-treatment promoted doxorubicin-induced LM3 cells apoptosis.Conclusion: The phosphorylation of eIF2 α promotes doxorubicin-induced hepatocellular carcinoma cell apoptosis.