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Exploring the underlying mechanism of oleanolic acid treating glioma by transcriptome and molecular docking
Jinxiang Huang1, Shengnan Lin2, Feng Zhu3
1Department of Neurosurgery, Shanghai Institute of Neurosurgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
Objective:
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.
Methods:
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.
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.
Conclusion:
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.
Insights
Oleanolic acid effectively inhibits glioma cell growth and invasion by inducing apoptosis. This study identified key molecular targets and pathways, offering new insights for developing novel anti-glioma drugs.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Gliomas are aggressive brain tumors with limited treatment options.
- Oleanolic acid shows potential as an anti-glioma therapeutic agent.
- The precise molecular mechanisms of oleanolic acid in glioma remain largely unknown.
Purpose of the Study:
- To investigate the anti-glioma effects of oleanolic acid.
- To elucidate the underlying molecular mechanisms of oleanolic acid in glioma treatment.
- To identify potential therapeutic targets for glioma.
Main Methods:
- In vitro assays (MTT, cell cloning, flow cytometry) assessed oleanolic acid's impact on glioma U251 cells.
- mRNA sequencing analyzed transcriptome changes in response to oleanolic acid treatment.
- Bioinformatic analyses (GO, KEGG, protein interaction) predicted molecular pathways and targets.
- Western blotting and molecular docking validated key findings.
Main Results:
- Oleanolic acid significantly inhibited glioma U251 cell proliferation, invasion, and colony formation while inducing apoptosis.
- mRNA sequencing identified 446 differentially expressed genes, with 96 upregulated and 350 downregulated.
- Oleanolic acid was found to modulate the TNF and NOD-like receptor signaling pathways.
- OAS2, OASL, IFIT3, RSAD2, and IRF1 were identified as potential core targets.
Conclusions:
- Transcriptome sequencing combined with molecular docking provides a robust method for predicting drug mechanisms.
- Oleanolic acid demonstrates significant anti-glioma activity through specific molecular pathways.
- This research offers novel insights for the development of oleanolic acid-based anti-glioma therapies.
