口腔医学研究

口腔医学研究 ›› 2017, Vol. 33 ›› Issue (12): 1241-1245.DOI: 10.13701/j.cnki.kqyxyj.2017.12.001

• 名家论道 •    下一篇

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

曾光,卫克文*   

  1. 第四军医大学唐都医院口腔科 陕西 西安 710038
  • 收稿日期:2017-05-26 出版日期:2017-12-20 发布日期:2018-01-03
  • 通讯作者: 卫克文,E-mail:weikewen1010@126.com
  • 作者简介:曾光(1982~ ),男,北京市人,博士,主治医师,讲师,主要从事抗肿瘤化合物研究。
  • 基金资助:
    国家自然科学基金(编号:81502337)；陕西省自然科学基金(编号:2015JM8486)

Effect of MAP4K3-mTOR Signaling in Licochalcone A-induced Autophagy and Apoptosis of Human Oral Squamous Cell Carcinoma Cells.

ZENG Guang,WEI Ke-wen*.   

  1. Department of Dentistry, Tangdu Hospital, The Forth Military Medical University, Xi’an 710038. China.
  • Received:2017-05-26 Online:2017-12-20 Published:2018-01-03

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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、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、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(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。

关键词: 甘草查尔酮A, 口腔鳞癌细胞, MAP4K3, mTOR信号通路, 自噬, 凋亡

Abstract: 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). Conclusion: 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.

Key words: Licochalcone A , Human oral squamous cell carcinoma cells (OSCC) , MAP4K3 , mTORsignaling Autophagy, Apoptosis

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