MAP4K3-mTOR信号在甘草查而酮A诱导的鳞癌细胞自噬与凋亡中的作用研究

发布时间：2018-03-17 00:10

本文选题：甘草查尔酮A　切入点：口腔鳞癌细胞　出处：《口腔医学研究》2017年12期 　论文类型：期刊论文

【摘要】：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、50μmol/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24h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、beclin1,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bcl-2蛋白表达水平(P0.05)。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(P0.05)。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(P0.05)。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。
[Abstract]:Aim: to investigate the role of MAP4K3-mTOR signal cascade in the autophagy and apoptosis of human oral squamous carcinoma cells induced by glycyrrhizin A. methods: human oral squamous cell carcinoma (SCC-25) cells were stimulated with 0 ~ 2550 渭 mol/L of glycyrrhizin A and collected at 0 ~ 6 and 24 h after stimulation. Western blot was used to detect the protein expression levels of MAP4K3AK ~ + -mTOR pathway, LC3-IIBbeclin1 and apoptosis marker caspase-3, caspase-9 and bcl-2, respectively. Results: glycyrrhizin A could decrease the expression of MAP4K3, p-mTOR and p-p70S6 protein in SCC-25 cells in a dose-and time-dependent manner, and promote the expression of caspase-3 and caspase-9 protein in SCC-25 cells. The expression of p-mTORcaspase-3 and caspase-9 protein increased significantly after lentivirus overexpression of MAP4K3, and the expression levels of LC3-IIBbeclin1 and bcl-2 protein decreased significantly. The number of early apoptosis and the number of early apoptosis in SCC-25 cells stimulated by licorice chalcone A were significantly decreased. The number of phase apoptosis was significantly higher than that of control group. This effect can be significantly enhanced by MAP4K3 overexpression. Conclusion: glycyrrhizin A can inhibit MAP4K3-mTOR signal cascade in a time-and dose-dependent manner, and promote autophagy and apoptosis of human oral squamous carcinoma cells. When overexpression of MAP4K3 activates mTOR signal cascade, The autophagy activity of squamous carcinoma cells was inhibited, but the apoptotic activity was significantly increased.
【作者单位】：第四军医大学唐都医院口腔科;
【基金】：国家自然科学基金(编号:81502337) 陕西省自然科学基金(编号:2015JM8486)
【分类号】：R739.8

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