RESUMO
Glioblastoma is a highly aggressive brain tumor characterized by high recurrence and poor prognosis. Vitexin has shown activities against esophageal, liver, lung, colorectal, and ovarian cancers; however, there is little knowledge on the activity of vitexin against glioblastoma. This study was therefore designed with aims to examine the effects of vitexin on proliferation, invasion, and apoptosis of human U251 glioblastoma cells and explore the underlying molecular mechanisms using mRNA sequencing and molecular docking. Vitexin was found to inhibit cell proliferation, colony formation, and invasion and promote apoptosis in U251 cells. mRNA sequencing identified 499 differentially expressed genes in vitexin-treated U251 cells relative to controls, including 154 upregulated genes and 345 downregulated genes. Gene ontology (GO) term enrichment analysis revealed that the upregulated genes were most significantly enriched in intrinsic apoptotic signaling pathway and the downregulated genes were most significantly enriched in positive regulation of cell development and positive regulation of locomotion relating to biological processes, endoplasmic reticulum lumen and side of membrane relating to cellular components, and receptor ligand activity and receptor regulator activity relating to molecular functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the upregulated genes were involved in the pathways of transcriptional misregulation in cancer and the downregulated genes were involved in FoxO and JAK/STAT signaling pathways. Western blotting assay revealed that vitexin treatment resulted in reduced p-JAK1, p-JAK3, and p-STAT3 protein expression in U251 cells relative to untreated controls, and molecular docking predicted that vitexin had docking scores of -8.8, -10.8, and -10.5 kJ/mol with STAT3, JAK1, and JAK2, respectively. The results of the present study demonstrate that vitexin inhibits the proliferation and invasion and induces the apoptosis of glioblastoma U251 cells through suppressing the JAK/STAT3 signaling pathway, and vitexin may be a promising potential agent for the chemotherapy of glioblastoma.
