He Xiuzhen, Dou Lu, Wang Jie, Xia Lili, Miao Jiawei, Yan Yongbo
Department of Basic Medicine, Chongqing Three Gorges Medical College, Chongqing, 404120, China.
Key Laboratory, Chongqing Three Gorges Medical College, Chongqing, 404120, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Feb;398(2):1483-1495. doi: 10.1007/s00210-024-03334-x. Epub 2024 Aug 5.
Nobiletin is an active compound extracted from citrus fruits. Research has indicated that nobiletin has a potential inhibitory effect on ovarian cancer (OV). However, the mechanism of action remains unclear. The OV A2780 cells were treated using nobiletin, cell viability was examined using a cell counting kit-8 experiment, and cell migration was examined with a wound healing experiment. Nobiletin targets were retrieved from target databases. Differentially expressed genes (DEG) and weighted gene co-expression network analysis (WGCNA) were conducted on GSE26712 (OV). The intersection of the critical genes for nobiletin's action on OV and gene enrichment and immune infiltration analyses were performed. The Cancer Genome Atlas-OV data and molecular docking helped validate the findings. After adding nobiletin, cell viability and migration significantly decreased (P < 0.01). A total of 88 nobiletin targets and 1288 DEG were identified. The intersection genes were enriched inflammatory response and response to hypoxia. The most related module obtained from WGCNA contained 414 genes (correlation coefficient = 0.77, P < 0.01). DPP4 and TXNIP were recognized as the hub genes. The abundance of macrophages M2 and mast cells activated significantly enhanced with increased DPP4 expression (P < 0.05). The binding energy between DPP4/TXNIP and nobiletin was - 7.012/ - 7.184 kcal/mol, forming 5/2 hydrogen bonds. Nobiletin effectively suppresses the viability and migration of OV A2780 cells. In this process, DPP4 and TXNIP are the key target, immune regulation, and oxidative stress playing significant roles.
诺米林是一种从柑橘类水果中提取的活性化合物。研究表明，诺米林对卵巢癌（OV）具有潜在的抑制作用。然而，其作用机制尚不清楚。使用诺米林处理OV A2780细胞，通过细胞计数试剂盒-8实验检测细胞活力，并用伤口愈合实验检测细胞迁移。从靶标数据库中检索诺米林的靶标。对GSE26712（OV）进行差异表达基因（DEG）和加权基因共表达网络分析（WGCNA）。对诺米林作用于OV的关键基因进行交集分析，并进行基因富集和免疫浸润分析。癌症基因组图谱-OV数据和分子对接有助于验证研究结果。添加诺米林后，细胞活力和迁移显著降低（P < 0.01）。共鉴定出88个诺米林靶标和1288个DEG。交集基因富集于炎症反应和低氧反应。从WGCNA获得的最相关模块包含414个基因（相关系数 = 0.77，P < 0.01）。DPP4和TXNIP被识别为枢纽基因。随着DPP4表达增加，巨噬细胞M2和活化肥大细胞的丰度显著增强（P < 0.05）。DPP4/TXNIP与诺米林之间的结合能为-7.012/-7.184千卡/摩尔，形成5/2个氢键。诺米林有效抑制OV A2780细胞的活力和迁移。在此过程中，DPP4和TXNIP是关键靶点，免疫调节和氧化应激发挥重要作用。
