Exploring the potential mechanism of artesunate in intervening with glioma cells with distinct therapeutic effects on the basis of transcriptome sequencing and network pharmacology

ABSTRACT: Artesunate possesses the potential of intervening with glioma, however, its pharmacological mechanisms remain unclarified. In this research, we aim to explore the regulatory mechanism of artesunate acting on glioma through constructing the interaction network of therapeutic effects-related genes of artesunate based on transcriptome sequencing data of glioma cells, and then verified by apoptosis staining and molecular docking at cellular level. In vitro cell activity and proliferation assay of two human glioma cell lines indicated that artesunate exerted more obvious inhibitory effects on the cell activity and proliferation of U87 cells than that of U251 cells. It could significantly promote apoptosis in U87 cells (P<0.01), while not in U251 cells (P>0.05), detected by using Hoechst and TUNEL cell apoptosis staining. Further, the differential expression gene sets between artesunate-sensitive and non-sensitive cell line, as well the therapeutic effects-related genes of artesunate were obtained, respectively, by transcriptome sequencing and differential data analysis using the lysis buffer of U87 and U251 cells before and after artesunate treatment. Then, key putative targets that related to therapeutic effects were screened by constructing the interaction network of differential genes of three above comparison groups, and calculating their topological characteristics. Pathway enrichment analysis showed that those key putative targets were significantly enriched in several signaling pathways that were closely associated with the main pathological changes of glioma, among which ATF4-DDIT3-PARP1 signaling axis, that was related with cell apoptosis, was the most enriched in. Molecular docking indicated that artesunate had fine binding affinities with ATF4 and DDIT3. Above all, this study preliminarily revealed that artesunate may induce the apoptosis and inhibited cell proliferation of glioma cells through regulating the abnormal alterations of corresponding proteins in ATF4-DDIT3-PARP1 signaling axis, which provided the novel scientific basis for its potential application in treating glioma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE217531 | GEO | 2025/11/08

REPOSITORIES: GEO