Nobiletin regulates the proliferation and migration of ovarian cancer A2780 cells via DPP4 and TXNIP.

ABSTRACT

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.