Wang Guanghui, Cheng Jianxiang, Yao Meizhen, Li Jing, Chen Ting, Zhang Jia, Du Wensheng, Chen Youguo
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, 215006, Suzhou, Jiangsu, China.
Department of Obstetrics and Gynecology, Affiliated Hospital of Xuzhou Medical University, No. 99 Huaihai West Road, Xuzhou, 221000, Jiangsu, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):3803-3815. doi: 10.1007/s00210-024-03492-y. Epub 2024 Oct 3.
Ovarian cancer stands as the foremost cause of mortality among gynaecological diseases globally, characterized by high morbidity and mortality. Pinocembrin, a flavonoid from natural plant sources, exhibits diverse pharmacological properties. Despite its known pharmacological activities, its specific role in ovarian cancer treatment remains scarcely reported, and its precise molecular mechanism remains elusive. This study integrates network pharmacology and molecular docking techniques to explore pinocembrin's potential mechanism in ovarian cancer treatment. The targets of pinocembrin were compiled from the several online databases. Ovarian cancer targets were identified using the GeneCards database, with common target genes determined by data aggregation. Protein-protein interactions were analysed using the STRING platform. Subsequent Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. Molecular docking assessed the binding affinity between potential targets and active compounds. Finally, target validity was verified through in vitro experiments. We identified 163 potential pinocembrin targets for ovarian cancer treatment. GO and KEGG analyses revealed pinocembrin's involvement in protein kinase activity, protein phosphorylation, protein kinase complexes and cancer pathways in ovarian cancer treatment. Molecular docking demonstrated strong binding affinity between pinocembrin and most potential target active sites. In vitro experiments suggested pinocembrin's potential to induce apoptosis in ovarian cancer cells through the AKT1-mTOR signalling pathway. This study comprehensively elucidates pinocembrin's potential targets and mechanisms against ovarian cancer, aiming to provide promising candidates for developing novel and effective alternative and/or complementary nutritional supplements for the clinical treatment of ovarian cancer.
卵巢癌是全球妇科疾病中导致死亡的首要原因，具有高发病率和高死亡率的特点。松属素是一种源自天然植物的黄酮类化合物，具有多种药理特性。尽管其具有已知的药理活性，但其在卵巢癌治疗中的具体作用鲜有报道，其精确的分子机制也尚不清楚。本研究整合网络药理学和分子对接技术，以探索松属素在卵巢癌治疗中的潜在机制。松属素的靶点从多个在线数据库中收集。利用GeneCards数据库确定卵巢癌靶点，并通过数据汇总确定共同的靶基因。使用STRING平台分析蛋白质-蛋白质相互作用。随后进行基因本体功能注释和京都基因与基因组百科全书通路分析。分子对接评估潜在靶点与活性化合物之间的结合亲和力。最后，通过体外实验验证靶点的有效性。我们确定了163个松属素治疗卵巢癌的潜在靶点。基因本体和京都基因与基因组百科全书分析表明，松属素在卵巢癌治疗中参与蛋白激酶活性、蛋白质磷酸化、蛋白激酶复合物和癌症通路。分子对接表明松属素与大多数潜在靶点活性位点之间具有很强的结合亲和力。体外实验表明，松属素具有通过AKT1-mTOR信号通路诱导卵巢癌细胞凋亡的潜力。本研究全面阐明了松属素抗卵巢癌的潜在靶点和机制，旨在为开发新型有效的替代和/或补充营养补充剂用于卵巢癌临床治疗提供有前景的候选药物。
