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目的:探索MAP4K3-mTOR信号级联在甘草查而酮A诱导的人口腔鳞癌细胞自噬与凋亡中的作用.方法:分别采用0、25、50 μmol/L甘草查尔酮A刺激人口腔鳞癌SCC-25系细胞,并于刺激后0、6及24 h收集细胞,采用Western blot检测MAP4K3、AKT、mTOR通路分子,细胞自噬标识分子LC3-Ⅱ、beclinl,以及细胞凋亡标记分子caspase-3、caspase-9及bcl-2等的蛋白表达水平,采用Annexin V-PI染色检测细胞凋亡状况.结果:甘草查尔酮A可剂量及时间依赖性地降低SCC-25细胞MAP4K3、p-mTOR及p-p70S6蛋白的表达水平,促进其LC3-Ⅱ、beclin1、caspase-3及caspase-9蛋白表达水平,并抑制其bel-2蛋白表达水平(P＜0.05).采用慢病毒过表达MAP4K3后,p-mTOR、caspase-3及caspase-9蛋白表达水平显著增高,LC3-Ⅱ、beclin1及bcl-2蛋白表达水平则显著降低(P＜0.05).经甘草查尔酮A刺激后,SCC-25细胞早期凋亡数与晚期凋亡数均较对照组显著增多,该效应可被MAP4K3过表达处理显著增强(P＜0.05).结论:甘草查尔酮A可时间剂量依赖地抑制MAP4K3-mTOR信号级联,并促进人口腔鳞癌细胞的自噬与凋亡,当过表达MAP4K3活化mTOR信号级联后,鳞癌细胞自噬活动受到抑制,但其凋亡活动则显著增强.“,”Objective:To investigate the effect of MAP4K3-mTOR signaling in licochalcone A-induced autophagy and apoptosis of human oral squamous cell carcinoma cells (OSCC).Methods:OSCC SCC-25 cells were adopted and treated once with licochalcone A for 0,6,and 24 h at 0,25 and 50 μM.The cells were harvested for further investigation.Western blot analysis was adopted to detect the protein expression of MAP4K3,AKT,mTOR,and autophagy marker molecules LC3-Ⅱ and beclin1,and apoptosis marker molecules caspase-3,caspase-9,and bcl-2.Annexin V-PI staining was used to detect the cell apoptosis.Results:Exposure of SCC-25 cells to licochalcone A dose-and time-dependently decreased the protein expression of MAP4K3,p-mTOR,and p-p70S6,and increased the protein expression of LC3-Ⅱ,beclin1,caspase-3,and caspase-9.When the MAP4K3 was overexpressed,the protein expressions of p-mTOR,caspase-3,and caspase-9 were increased,while the expressions of LC3-Ⅱ,beclin1,and bcl-2 were decreased (P＜0.05).In addition,licochalcone A stimulation increased the number of early and late apoptotic SCC-25cells,which could be obviously reversed by MAP4K3 overexpression (P＜ 0.05).Conclsion:Licochalcone A dose-and time-dependently decreased MAP4K3-mTOR signaling,but increased the autophagy and apoptosis of SCC-25 cells.When MAP4K3 was overexpressed,the licochalcone A-induced autophagy decreased,but licochalcone A-induced apoptosis increased.