基于网络药理学探讨橙皮苷抗口腔鳞状细胞癌作用机制  

The mechanism of hesperidin against oral squamous cell carcinoma based on network pharmacology

作　　者：刘帅 李霄 张涛[2] 李国林 LIU Shuai;LI Xiao;ZHANG Tao;LI Guolin(Affiliated Stomatological Hospital,Jiamusi University,China,154000;Department of Basic Medicine,Jiamusi Univerisity;Department of Stomatology,Shanghai Eighth People's Hospital)

机构地区：[1]佳木斯大学附属口腔医院,154000 [2]佳木斯大学基础医学院 [3]上海市第八人民医院口腔科

出　　处：《实用口腔医学杂志》2024年第3期323-329,共7页Journal of Practical Stomatology

基　　金：上海市自然科学基金(编号:19ZR1438300);黑龙江省自然科学基金(编号:H201841)。

摘　　要：目的:探究橙皮苷对人舌鳞状细胞癌Tca-8113细胞的抑制作用并探索其作用机制。方法:用不同浓度橙皮苷体外培养人舌鳞状细胞癌Tca-8113细胞。MTT实验检测细胞增殖活性;流式细胞术检测细胞凋亡。网络药理学预测橙皮苷作用于Tca-8113细胞的潜在靶点;构建蛋白质蛋白质互作网络(PPI);进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。Q-PCR检测不同浓度橙皮苷对Tca-8113细胞相关mRNA表达水平的影响;分子对接预测橙皮苷与核心靶点的结合能,评分函数来判断结合能强弱。结果:橙皮苷对Tca-8113细胞显示浓度依赖性增殖抑制和促凋亡作用(P<0.05);KEGG富集分析橙皮苷调控口腔鳞状细胞癌涉及的关键基因靶点可能与PI3K-Akt、MAPK和Ras等信号通路有关;Q-PCR结果显示MAPK8、HSP90AA1和MAPK1(ERK2)的mRNA表达水平差异具有统计学意义(P<0.05);分子对接结果显示橙皮苷与MAPK1(ERK2)结合力最强。结论:橙皮苷可能通过调控Ras/Raf/MEK/ERK信号通路抑制Tca-8113细胞增殖并促进凋亡。Objective:To explore the effects of hesperidin against human tongue squamous cell carcinoma Tca-8113 cells and explore its mechanism of action.Methods:Tca-8113 cells were cultured in vitro with different concentrations of hesperidin.MTT assay and flow cytometry were used to detect the cell proliferation and apoptosis respectively.The potential targets of hesperidin against Tca-8113 cells were studied by network pharmacology.The protein-protein interaction network(PPI)was constructed,gene ontology GO analysis,kyoto gene and genome baike encyclopedia(KEGG)enrichment analysis were performed.Q-PCR was used to detect the effect of different concentrations of hesperidin on the related mRNA expression level of Tca-8113 cells.The binding force of hesperidin to the core targets was predicted by molecular docking and a scoring function was used to judge the binding force.Results:Hesperidin inhibited proliferation and promoted apoptosis of Tca-8113 cells(P<0.05)in a dosedependant manner;KEGG enrichment analysis of the key gene targets involved in the regulation of oral squamous cell carcinoma by hesperidin may be related to PI3K-Akt,MAPK and Ras signaling pathways.Q-PCR results showed that the mRNA expression of MAPK8,HSP90AA1 and MAPK1(ERK2)were significantly different(P<0.05).Molecular docking results showed that hesperidin had the strongest binding force with MAPK1(ERK2).Conclusion:Hesperidin may inhibit the proliferation and promote apoptosis of Tca-8113 cells by regulating Ras/Raf/MEK/ERK signaling pathway.

关 键 词：橙皮苷 口腔鳞状细胞癌 网络药理学 分子对接 

分 类 号：R739.8[医药卫生—肿瘤]