Abstract：
Ovarian cancer (OC) is a common malignancies of the female genitalia. P. montana var. lobata (Willd.), a herb with anti-tumor effects, is widely used in the clinical treatment of ovarian cancer (OC), but the ingredients and molecular mechanism of action remains to be explored. In this study, we extracted the main active ingredients of P. montana var. lobata (Willd.) from the TCMSP database, and predicted its potential targets of action against OC from the DisGeNET and GeneCards databases. Protein-protein interaction (PPI) was constructed using the STRING database, while pathway enrichment analyses were performed using the DAVID database. Next, we generated an Ingredient-Target-Pathway network using Cytoscape 3.7.2, then processed the key targets of action and main active ingredients for molecular docking. The results showed that seven active ingredients of P montana var. lobata (Willd.) were associated with treating for OC, namely beta-sitosterol, coumestrol, daidzein, formononetin, genistein, puerarin and scoparone, two important targets Casp3 and Jun, and signaling pathways of P. montana var. lobata (Willd.) against the progression of OC. TUNEL staining, enzyme-linked immunosorbent assay (ELISA), and Western blot assays, the pharmacodynamic effect of puerarin in the treatment of OC and the major targets were verified. Animal experiment demonstrated that application of puerarin at different times of modeling not only upregulated expression of Casp3, Smac, and c-jun proteins, but also promoted apoptosis in tumor cells, hence inhibiting progression of OC. This study demonstrates that P. montana var. lobata (Willd.) can thereby induce apoptosis in tumor cells and inhibit malignant progression through activating expression of Casp3, smac, and c-jun proteins to regulate related apoptosis pathways, as validated by network pharmacology predictions and animal experiments, and can be verifed by large-scale clinical trials in the future. This study also provides theoretical support and new research perspectives for this disease.
摘要：
卵巢癌（OC）是女性生殖器的常见恶性肿瘤。P.蒙大拿州var。洛巴塔(威尔德。),一种具有抗肿瘤作用的草药，广泛应用于卵巢癌的临床治疗,但作用的成分和分子机制仍有待探索。在这项研究中,我们提取了蒙大拿var的主要活性成分。洛巴塔(威尔德。)来自TCMSP数据库，并从DisGeNet和GeneCards数据库中预测了其针对OC的潜在行动目标。使用STRING数据库构建蛋白质-蛋白质相互作用(PPI)，而使用DAVID数据库进行途径富集分析.接下来,我们使用Cytoscape3.7.2生成了一个成分-目标-途径网络,然后对关键作用靶点和主要活性成分进行了分子对接处理.结果表明，蒙大拿的7种活性成分var。洛巴塔(威尔德。)与治疗OC有关，即β-谷甾醇，coumestrol,Daidzein,福蒙素,Genistein,葛根素和soparone,两个重要目标Casp3和Jun，和P.montanavar的信号通路。洛巴塔(威尔德。)反对OC的发展。TUNEL染色,酶联免疫吸附测定(ELISA),和蛋白质印迹分析，对葛根素治疗OC的药效学作用及主要作用靶点进行了验证。动物实验表明,在造模不同时期应用葛根素不仅上调了Casp3、Smac、和c-jun蛋白,而且还促进肿瘤细胞的凋亡，因此抑制OC的进展。这项研究表明，蒙大拿州变种。洛巴塔(威尔德。)可以通过激活Casp3、smac、和c-jun蛋白调节相关的凋亡途径，通过网络药理学预测和动物实验验证，并且可以通过未来的大规模临床试验来验证。本研究也为本病提供了理论支持和新的研究视角。
