Sanami Samira, Aghaamoo Shahrzad, Ahmad Sajjad, Fazli Ali, Mansouri Bahareh, Nobre Oliveira Jonas Ivan, Rahmanian Mojgan
Abnormal Uterine Bleeding Research Center, Semnan University of Medical Sciences, Semnan, Iran.
Department of Health and Biological Sciences, Abasyn University, Peshawar, Pakistan.
PLoS One. 2025 Sep 12;20(9):e0330841. doi: 10.1371/journal.pone.0330841. eCollection 2025.
Endometriosis is characterized by the presence of endometrial tissue outside the uterine cavity. The administration of drugs designated for this condition has significant adverse effects, such as signs of estrogen insufficiency and suppression of ovulation. Considering this issue, this study aims to employ drugs repurposing approaches for the treatment of endometriosis. The GSE120103 dataset was selected to assess the expression of genes involved in endometriosis, then differentially expressed genes (DEGs) were identified using the "Limma" package in R Studio. Functional and pathway enrichment analysis of 708 up-regulated and 414 down-regulated DEGs was performed using ShinyGO 0.81 and DAVID tools. the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) was then used to build a protein-protein interaction (PPI) network of up-regulated DEGs, followed by Cytoscape software to identify hub genes. Vascular endothelial growth factor receptor 2 (VEGFR2) and interleukin-6 (IL-6) were identified as hub genes, assessments suggested that VEGFR2 may be a more promising possibility for druggability than IL-6. 16 FDA-approved drugs targeting VEGFR2 were identified, and molecular docking analysis indicated that ponatinib (-9.6 kcal/mol) had a more favorable binding energy than the co-crystal ligand (-9.2 kcal/mol). Moreover, molecular dynamics (MD) simulation analysis demonstrated considerable stability of the VEGFR2-ponatinib complex over a 100 nanoseconds (ns) timescale. The findings of this study indicate that ponatinib may provide considerable therapeutic promise for the treatment of endometriosis. Nevertheless, additional experimental investigations are required to evaluate its therapeutic efficacy.
子宫内膜异位症的特征是子宫腔外存在子宫内膜组织。用于治疗这种疾病的药物具有显著的副作用，如雌激素不足的症状和排卵抑制。考虑到这一问题，本研究旨在采用药物重新利用方法来治疗子宫内膜异位症。选择GSE120103数据集来评估参与子宫内膜异位症的基因表达，然后使用R Studio中的“Limma”软件包识别差异表达基因（DEG）。使用ShinyGO 0.81和DAVID工具对708个上调和414个下调的DEG进行功能和通路富集分析。然后使用检索相互作用基因/蛋白质的搜索工具（STRING）构建上调DEG的蛋白质-蛋白质相互作用（PPI）网络，随后使用Cytoscape软件识别枢纽基因。血管内皮生长因子受体2（VEGFR2）和白细胞介素-6（IL-6）被确定为枢纽基因，评估表明VEGFR2在可成药方面可能比IL-6更具潜力。确定了16种FDA批准的靶向VEGFR2的药物，分子对接分析表明泊那替尼（-9.6 kcal/mol）比共晶配体（-9.2 kcal/mol）具有更有利的结合能。此外，分子动力学（MD）模拟分析表明，VEGFR2-泊那替尼复合物在100纳秒（ns）的时间尺度上具有相当的稳定性。本研究结果表明，泊那替尼可能为子宫内膜异位症的治疗提供可观的治疗前景。然而，需要进一步的实验研究来评估其治疗效果。
