基于数据库和网络药理学探索槟榔诱导口腔黏膜下纤维性变向口腔鳞癌转变的机制  

Mechanism of Areca catechu L.inducing the transformation of oral submucous fibrosis to oral squamous cell carcinoma based on data mining and network pharmacology

作　　者：张婧 林琳 张磊[3] 尹雪雯 浦迎秋[1] ZHANG Jing;LIN Lin;ZHANG Lei;YIN Xuewen;PU Yingqiu(Department of Pharmacy,Nanjing Stomatological Hospital,Affiliated Hospital of Medical School,Institute of Stomatology,Nanjing University,Nanjing 210008,China)

机构地区：[1]南京大学医学院附属口腔医院、南京市口腔医院药学部、南京大学口腔医学研究所,南京210008 [2]南京大学医学院附属口腔医院、南京市口腔医院口腔黏膜病科、南京大学口腔医学研究所,210008 [3]南京大学医学院附属口腔医院、南京市口腔医院口腔病理科、南京大学口腔医学研究所,210008

出　　处：《临床肿瘤学杂志》2024年第9期833-838,共6页Chinese Clinical Oncology

基　　金：南京市卫生科技发展资助项目(YKK23182)。

摘　　要：目的探讨槟榔诱导口腔黏膜下纤维性变(OSF)转变为口腔鳞癌(OSCC)的生物学过程,为进一步验证潜在的精准生物标记物和靶点奠定基础。方法应用生物信息学的分析方法,从GeneCards、OMI、DisGENET数据库获得发病基因,从TCMSP和Batman-TCM数据库获得槟榔活性成分相关作用靶点,在活性成分靶点的互作网络基础上筛选出核心靶点进行富集分析,探究靶点的潜在生物学功能并依据蛋白靶点序列相似性获得同源功能注释。通过苏木精伊红染色法观察OSCC和OSF组织病理改变并进行Western blotting验证。结果本研究筛选出槟榔24个活性成分参与促进OSF进展为OSCC的101个关键靶点。富集分析显示,细胞周期、血管生成和上皮间质转换等具有统计学意义的通路28个,蛋白聚类簇注释到17个功能分类。对功能富集分析显著性的通路结合文献报道,选取磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(Akt)通路进行验证,OSCC/OSF+组织的PI3K和Akt表达量高于OSCC/OSF-组织(P<0.05)。结论本研究初步筛选出槟榔活性成分在OSF向OSCC进展中的关键分子和靶点,OSCC发病机制众多且复杂,PI3K/Akt通路在OSF转变为OSCC病理过程中具有重要作用,可能成为早期干预或治疗的新靶点。Objective To explore the biological process of the transformation of oral submucosal fibrosis(OSF)into oral squamous cell carcinoma(OSCC)induced by Areca catechu L.,and lay a foundation for further validation as biomarkers and targets for precision medicine.Methods By applying bioinformatics analysis methods,pathogenic genes were obtained from GeneCards,OMI and DisGENET databases,and relevant action targets of Areca catechu L.active ingredients were obtained from TCMSP and Batman-TCM databases.Core targets were screened out for enrichment analysis based on the interaction network between active ingredients and targets.Pathological changes of OSCC and OSF were observed by hematoxylin-eosin staining and verified by Western blotting.Results In this study,24 active ingredients of Areca catechu L.were selected to participate in 101 key targets for promoting OSF progression to OSCC.Enrichment analysis showed 28 statistically significant pathways such as cell cycle,angiogenesis and epithelial-mesenchymal transition,and 17 functional classifications were annotated by protein clusters.The phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway with significant functional enrichment analysis was selected for verification based on literature reports.Western blotting analysis showed that OSCC/OSF+significantly increased the expression levels of PI3K and Akt compared with OSCC/OSF-(P<0.05).Conclusion The key molecules and targets of Areca catechu L.active ingredient in the progression from OSF to OSCC were initially screened out.The pathogenesis of OSCC was numerous and complex.PI3K/Akt pathway plays an important role in the pathological process of OSF transformation into OSCC,which may be a new target for early intervention or treatment.

关 键 词：口腔鳞状细胞癌 口腔黏膜下纤维性变 槟榔 网络药理学 磷脂酰肌醇-3激酶/蛋白激酶B通路 

分 类 号：R739.85[医药卫生—肿瘤]