抑制自噬促进MK-2206诱导SGC-7901胃癌细胞发生DNA损伤  

Blocking autophagy magnifies MK-2206-induced DNA damage in SGC-7901 cells

作　　者：张翠[1] 姜文艳[1] 吴玉梅[2] 庄梦玮 王西双 焦鹏[3] 

机构地区：[1]泰山医学院生命科学学院,山东泰安271016 [2]胜利油田机关医院药剂科,山东东营257000 [3]泰山医学院生命科学研究中心,山东泰安271016

出　　处：《中国病理生理杂志》2015年第9期1545-1549,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81272683);山东省自然科学基金资助项目(No.ZR2014HL107);泰安市科技发展计划项目(No.201440774-14)

摘　　要：目的:探讨蛋白激酶B(protein kinase B,Akt)抑制剂MK-2206对胃癌细胞SGC-7901DNA损伤的影响。方法:不同浓度的MK-2206作用于SGC-7901细胞后,免疫荧光检测细胞内DNA损伤标记分子磷酸化组蛋白H2AX(γ-H2AX)焦点的生成,Western blot检测DNA损伤相关蛋白的表达水平,同时观察MK-2206对自噬标志蛋白LC3-II表达量的影响,用以确定MK-2206是否促进细胞发生自噬。结果:MK-2206能够诱导SGC-7901细胞发生DNA损伤,促进细胞内γ-H2AX焦点生成,并且激活DNA损伤相关蛋白的表达;MK-2206作用细胞后,LC3-II的生成增加;抑制细胞的自噬显著增强了MK-2206诱导的H2AX磷酸化水平。结论:Akt抑制剂MK-2206能够诱导细胞发生DNA损伤和自噬,抑制自噬促进了MK-2206诱导的DNA损伤。AIM：To investigate the effect of MK-2206, an inhibitor of protein kinase B （Akt）, on the DNA damage of SGC-7901 cells.METHODS： SGC-7901 cells were treated with different concentrations of MK-2206, and phosphorylated histone H2AX （γ-H2AX） foci formation was detected by immunofluorescence staining .Western blot analy-sis was used to exam the levels of DNA damage-related protein.The expression of LC3-Ⅱ was determined to evaluate the change of autophagy .RESULTS：MK-2206 treatment increased the formation of γ-H2AX foci and histone H2AX phospho-rylation in the SGC-7901 cells.The levels of DNA damage response protein were also increased .In addition, MK-2206-treated SGC-7901 cells increased the expression of LC 3-II, a hallmark of autophagy .Inhibition of autophagy significantly enhanced MK-2206-mediated histone H2AX phosphorylation.CONCLUSION：MK-2206 induces DNA damage and auto-phagy in SGC-7901 cells.Blocking autophagy potentiates the response of MK-2206-induced DNA damage .

关 键 词：MK-2206 Akt抑制剂 DNA损伤 Γ-H2AX 细胞自噬 

分 类 号：R730.23[医药卫生—肿瘤] R735.2[医药卫生—临床医学]