Exploring the mechanism of baicalein on choroid melanoma based on network pharmacology, transcriptomics and...

Baicalein (BAI), a flavonoid from Scutellaria baicalensis, exhibits therapeutic potential across inflammation, viral infections, and cancers. Yet, its role in choroidal melanoma (CM), the most common intraocular malignancy, remains poorly understood. The aim of this study was to investigate BAI's anti-CM effects and underlying mechanisms by integrating network pharmacology, transcriptomic analyses, and experimental validation.

Network pharmacology, molecular docking and transcriptomic analysis were used to identify potential targets and signaling pathways. The anti-tumor effect of baicalein was verified through combined intracellular and extracellular experiments. Western blotting was used to analyse the effects of BAI and IGF-1 co-treatment on the phosphorylation level of the pathway and its downstream cycling, apoptosis and migration related proteins.

Integrated analyses implicated the inhibitory effect of BAI on choroidal melanoma may be related to the cell cycle, apoptosis and critical signaling pathways, particularly the PI3K/AKT/mTOR axis. In vitro experiments have proved that BAI can inhibit the proliferation and migration of C918 and OCM-1 cells, induce cell cycle arrest, and simultaneously trigger mitochondrial-mediated apoptosis and oxidative stress injury. Similar results were observed in the allograft tumor model of C918. IGF-1 pretreatment attenuated BAI's effects, confirming pathway dependency.

Our study demonstrates for the first time that BAI can inhibit CM malignant progression by modulating the PI3K/AKT/mTOR signaling pathway. This study suggests that BAI may be used as a promising anti-tumor agent for further treatment of CM.