Identification of potential molecular targets of luteolin in the treatment of hepatocellular carcinoma based on network pharmacology and transcriptome sequencing technology

Objective: This study aims to identify potential target genes of luteolin (LUT) for treating hepatocellular carcinoma (HCC) through integrated in vitro experiments, network pharmacology, bioinformatics, and transcriptome Sequencing (RNA-seq).

Methods: Potential LUT-associated therapeutic targets for HCC were predicted using network pharmacology. The anti-HCC effects of LUT were evaluated in vitro by assessing its impact on SMMC-7721 and HepG2 cell viability, Apoptosis, migration, and invasion. Transcriptome Sequencing was performed to identify differentially expressed genes (DEGs) in LUT-treated HepG2 cells, followed by bioinformatics analyses to validate hub targets and their associated pathways.

Result: Network pharmacology predicted 100 potential protein targets of LUT for HCC treatment, implicating pathways related to inflammation, cell migration, cell cycle regulation, and Apoptosis, including the HIF-1α signaling axis. In vitro experiments demonstrated that LUT (40, 60, and 90 µmol·L^-¹) significantly inhibited proliferation, induced Apoptosis, and suppressed migration and invasion in SMMC-7721 and HepG2 cells. Transcriptome analysis identified 975 DEGs in LUT-treated HepG2 cells, with MMP9 and Src emerging as key targets. Bioinformatics validation further linked LUT's anti-HCC effects to cell cycle modulation, wound healing, enzyme inhibition, and the TNFα and HIF-1 signaling pathways.

Conclusion: LLUT suppresses HCC progression by inhibiting proliferation, regulating cell cycle and Apoptosis, and blocking invasion and migration. Its therapeutic mechanisms likely involve targeting MMP9 and modulating the HIF-1α signaling pathway.