Ferroptosis-related genes are involved in the activity of resveratrol against esophageal cancer

Abstract

Abstract Ferroptosis is an iron-dependent programmed cell death closely associated with cancer oncogenesis, and resveratrol could regulate ferroptosis resulting in an anticancer effect. However, how resveratrol regulates ferroptosis leading to anticancer activity in esophageal cancer (ESCA) has not been studied. The targets related to resveratrol, ferroptosis, and ESCA were obtained from databases. The hub targets for resveratrol regulating ferroptosis in ESCA were identified from the protein-protein interaction (PPI) network and performed by functional enrichment analysis. Furthermore, we analyzed the TP53 gene by the Kaplan-Meier Plotter, TIMER2.0, UALCAN, cBioPortal and CAMOIP databases. Finally, the potential targets and mechanisms were validated through in vitro experiments. We screened 43 targets from the databases, with central targets covering TP53, STAT3, PTGS2, RELA, and SRC. The key target for resveratrol regulating ferroptosis-related genes in ESCA was mutant TP53, which was correlated with immune infiltration in ESCA. Validated experiments showed that resveratrol possessed potent activity against ESCA cell line and decreased the cell migration capacity of KYSE30 cells. RT-qPCR results indicated that resveratrol down-regulated the expression of TP53, CCND1, CDK2, STAT3, IL-6, and AKT and up-regulated CDKN1A expression. In conclusion, our data suggest that resveratrol suppressed ESCA by regulating ferroptosis-related genes, such as mutant TP53, and is through signaling pathways involving TP53, STAT3/IL-6, AKT, and the cell cycle, advancing our understanding of the anticancer effect of resveratrol.