Zhang Qianqian, Huang Xianghua
Department of Gynecology, Hebei Medical University Second Affiliated Hospital, Shijiazhuang, China.
PeerJ. 2021 Aug 24;9:e11995. doi: 10.7717/peerj.11995. eCollection 2021.
is a traditional Chinese medicine and has been used for adjuvant clinical therapy for a variety of cancers. However, the mechanism of its action on endometrial carcinoma is unclear. Based on the Gene Expression Omnibus (GEO) database, the Cancer Genome Atlas (TCGA) database, and the Traditional Chinese Medicine System Pharmacology Database (TCMSP™), the drug and target compounds were initially screened to construct a common network module. Twenty active compounds in were successfully identified, which hit by 463 potential targets related to endometrial cancer. Eight of the more highly predictive compounds (such as Jaranol, Bifendate, Isorhamnetin, Calycosin, 7-O-methylisomucronulatol, Formononetin, Kaempferol, Quercetin) were involved in DNA integrity checkpoint, cyclin-dependent protein kinase holoenzyme complex, and histone kinase activity. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway confirmed that might play a role in the treatment of endometrial cancer through p53 signalling pathway, transcriptional misregulation in cancer, and endometrial cancer signalling pathway. Drug-target-pathway networks were constructed using Cytoscape to provide a visual perspective. In addition, we verified that formononetin inhibited the proliferation of endometrial cancer cells through cell viability tests and clone formation tests. And qPCR and western blot found that formononetin exerts anti-cancer effects by promoting the expression of estrogen receptor beta (ER) and p53. Based on a systematic network pharmacology approach, our works successfully predict the active ingredients and potential targets of for application to endometrial cancer and helps to illustrate mechanism of action on a comprehensive level.
是一种传统中药，已用于多种癌症的临床辅助治疗。然而，其对子宫内膜癌的作用机制尚不清楚。基于基因表达综合数据库（GEO）、癌症基因组图谱（TCGA）数据库和中药系统药理学数据库（TCMSP™），初步筛选药物和靶标化合物以构建共同的网络模块。成功鉴定出其中的20种活性化合物，它们作用于463个与子宫内膜癌相关的潜在靶点。8种预测性较高的化合物（如紫铆醇、联苯双酯、异鼠李素、毛蕊异黄酮、7-O-甲基异微绒毛醇、芒柄花素、山柰酚、槲皮素）参与了DNA完整性检查点、细胞周期蛋白依赖性蛋白激酶全酶复合物和组蛋白激酶活性。此外，基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路证实，可能通过p53信号通路、癌症中的转录失调和子宫内膜癌信号通路在子宫内膜癌治疗中发挥作用。使用Cytoscape构建药物-靶标-通路网络以提供直观视角。此外，我们通过细胞活力测试和克隆形成测试验证了芒柄花素抑制子宫内膜癌细胞的增殖。并且qPCR和蛋白质印迹发现芒柄花素通过促进雌激素受体β（ER）和p53的表达发挥抗癌作用。基于系统的网络药理学方法，我们的工作成功预测了用于子宫内膜癌的活性成分和潜在靶点，并有助于在综合层面阐明其作用机制。
