Oleanolic acid is a promising drug for treating gliomas, but its underlying mechanism is unclear. This study aimed to determine the potential effect of oleanolic acid on glioma and its mechanism.

Firstly, the effects of oleanolic acid on the proliferation, invasion, and apoptosis of glioma U251 cells were detected by in vitro experiments such as MTT assay, cell cloning, and flow cytometry. The transcriptome data of U251 cells treated with oleanolic acid and untreated were sequenced by mRNA, and then the differentially expressed genes were analyzed by gene ontology (GO), genomic encyclopedia (KEGG) pathway enrichment analysis, and protein interaction topology analysis. The underlying mechanism of oleanolic acid was predicted, and the related protein interaction network was constructed. Finally, Western blotting and molecular docking techniques verified the mRNA sequencing results.

Oleanolic acid could effectively inhibit the proliferation, colony formation, and invasion of U251 cells and induce apoptosis. A total of 446 differentially expressed genes were detected by mRNA sequencing, of which 96 genes were up-regulated and 350 down-regulated. Oleanolic acid induces the TNF signal pathway and NOD-like receptor signal pathway at the intracellular level. In addition, OAS2, OASL, IFIT3, RSAD2, and IRF1 may be the core targets of oleanolic acid in treating glioma.

Transcriptome combined with molecular docking technique is used to predict the possible mechanism of oleanolic acid in the treatment of glioma, which provides new ideas and insights for developing and researching antitumor drugs.