基于网络药理学的昆仑雪菊总黄酮对食管癌细胞的抗瘤作用  

Anti-tumor effect of Kunlun Chrysanthemum flavonoids on esophageal cancer cells based on network pharmacology

作　　者：乔魏 荆新鑫 李明[1] 尚帅 吴桂霞[2] QIAO Wei;JING Xinxin;LI Ming;SHANG Shuai;WU Guixia(The Fifth Clinical Medical College,Xinjiang Medical University,Urumqi 830011,China;School of Pre-clinical Medicine,Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]新疆医科大学第五临床医学院,乌鲁木齐830011 [2]新疆医科大学基础医学院,乌鲁木齐830011

出　　处：《新疆医科大学学报》2019年第9期1216-1222,共7页Journal of Xinjiang Medical University

基　　金：新疆维吾尔自治区自然科学基金(2019D01C218);新疆医科大学大学生创新计划项目(CX201703)

摘　　要：目的探讨昆仑雪菊总黄酮对食管癌的抗瘤作用及可能的分子机制。方法用不同浓度的雪菊总黄酮提取物与Eca 109细胞共孵育后,光镜观察Eca 109细胞形态的变化,噻唑蓝(MTT)法检测雪菊总黄酮对Eca 109细胞的生长抑制作用;应用中药系统药理数据库和分析平台(TCMSP)及在线《人类孟德尔遗传》(OMIM)数据库查找雪菊总黄酮成分、靶点及食管癌的相关靶点信息,Cytoscape3.2.6软件进行网络构建、分析及可视化工作,构建雪菊总黄酮-靶点-食管癌网络模型,通过DAVID网站进行关键靶点的日本京都基因与基因组百科全书(KEGG)通路富集分析。结果光镜及MTT结果显示,雪菊总黄酮明显抑制了Eca 109细胞的生长;通过TCMSP数据库找到总黄酮2个主要活性化合物的78个靶点;通过OMIM数据库找到食管癌相关靶点并进行扩展,取高于2倍平均节点度的靶点共141个;将化合物及食管癌靶点映射交集后找到表皮生长因子(EGFR)、Bcl-2、TP53、GSK3B等13个关键靶点,KEGG通路富集分析显示,雪菊总黄酮对食管癌的抗瘤作用可能与影响细胞分裂增殖、凋亡、血管生成等生物学过程有关。进一步通过Western blot进行细胞实验的验证结果表明,雪菊总黄酮明显下调了Bcl-2的表达,诱导了细胞的凋亡。结论雪菊总黄酮对食管癌的抗瘤作用是多靶点、多途径的,PI3K/Akt信号通路可能发挥关键作用。Objective To explore the anti-tumor effect and possible mechanism of total flavonoids of Kunlun Chrysanthemum on esophageal cancer based on network pharmacology. Methods The morphological changes and growth inhibition of Eca 109 cell were observed under light microscopy and through MTT method after Eca 109 cells incubated with different concentrations of chrysanthemum flavonoids. Application of TCMSP and OMIM database to investigate composition, targets of Kunlun Chrysanthemum flavonoids and targets information of esophageal cancer. Network, analysis and visualization were built up by Cytoscape3.2.6. Chrysanthemum flavonoids-targets-esophageal network was builded. Using DAVID to predict key targets and KEGG pathway enrichment analysis. Results The results of light microscopy and MTT showed that the flavonoids significantly inhibited the growth of Eca 109 cells. Seventy-eight targets of two main active compounds of flavonoids were found by TCMSP database. The OMIM database was used to find targets of esophageal cancer, after expanding, 141 targets were selected with an average nodal degree higher than 2 times. After the intersection, we obtained 13 main targets, such as EGFR, Bcl-2, TP53, GSK3 B. KEGG pathway enrichment analysis showed that the anti-tumor effect of chrysanthemum flavonoids may be related to influence cell biological processes such as proliferation, apoptosis, angiogenesis. The results of Western blot showed that total flavonoids significantly decreased the expression of Bcl-2 and promoted apoptosis. Conclusion The anti-tumor effect of flavonoids of chrysanthemum on esophageal cancer is multi-target and multi-pathway, and the PI3 K/Akt signaling pathway may play a key role.

关 键 词：昆仑雪菊 总黄酮 食管癌 抗瘤 网络药理学 

分 类 号：R932[医药卫生—生药学]