Neuroglobin promotes the proliferation and suppresses the apoptosis of glioma cells by activating the PI3K/AKT pathway

Abstract

Our previous study demonstrated that neuroglobin (Ngb) functions as an independent predictive indicator of the prognosis of patients with glioma and promotes cancer cell growth by suppressing apoptosis. However, the understanding of the mechanisms underlying the survival‑enhancing function of Ngb in glioma is limited. In the present study, KEGG PathwayFinder by gene correlation analysis was performed on the R2: Genomics Analysis and Visualization Platform, which revealed a high association between Ngb and the phosphatidylinositol 3‑kinase (PI3K)/AKT pathway using glioma data (GSE4290) from the Gene Expression Omnibus database. Furthermore, western blotting experiments were performed in U251 and U87 glioma cells, and Ngb knockdown using short hairpin RNA reduced the protein levels of phosphorylated (p)‑AKT, p‑mammalian target of rapamycin (mTOR) and antiapoptotic factor Bcl‑2, and increased the expression of the proapoptotic protein Bcl‑2‑associated X, in U251 cells. In addition, Ngb overexpression promoted the activation of the PI3K/AKT pathway in U87 cells. MK2206, a PI3K/AKT signaling inhibitor, reduced the expression of p‑AKT and increased the levels of apoptosis‑associated proteins, including cleaved poly(ADP‑ribose) polymerase 1 and cleaved caspase‑3/7/8, in Ngb‑overexpressing U87 cells. Furthermore, MK2206 treatment reduced the proliferation and induced the apoptosis of Ngb‑overexpressing U87 cells, as indicated by the results of MTT, colony formation and flow cytometry assays. In addition, insulin‑like growth factor‑1, a PI3K/AKT signaling activator, reversed Ngb knockdown‑induced growth arrest and apoptosis in U251 cells. In conclusion, the results of the present study indicate that Ngb may facilitate a malignant phenotype of glioma cells by activating the PI3K/AKT pathway.