Icaritin inhibits glioblastoma cell viability and glycolysis by blocking the IL-6/Stat3 pathway

Glioblastoma (GBM) is a common and aggressive brain tumor that is associated with significant increase in glycolysis for energy production. Icaritin is a natural compound and exhibits anticancer activity in GBM. However, the effect of icaritin on glycolysis in GBM cells remains unclear. The aim of the current study was to investigate the effect of icaritin on glycolysis in GBM cells. The human GBM cell lines U87 and T98G were treated with icaritin or the inhibitor of Stat3 (S3I-201) in the presence or absence of recombinant human interleukin (IL)-6. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. The glycolysis was analyzed by detecting the glucose consumption and lactate production. The Western blot analysis was conducted to detect the expressions of hexokinase 2 (HK2), signal transducer and activator of transcription 3 (Stat3), p-Stat3, and B lymphoma Mo-MLV insertion region 1 (Bmi-1). Results showed that icaritin inhibited the viability of U87 and T98G cells in a dose-dependent manner. The decreased glucose consumption and lactate production, accompanied by reduced expressions of HK2, were found in both U87 and T98G cells. Icaritin inhibited the IL-6/Stat3 pathway, which is evidenced by the decreased expressions of p-Stat3 and Bmi-1. IL-6 treatment induced the phosphorylation of Stat3 and Bmi-1 expression, increased cell viability, as well as elevated glucose consumption, lactate production, and HK2 expression; however, the effects of IL-6 were attenuated by icaritin or S3I-201 treatment. In conclusion, icaritin exerted inhibitory effects on cell viability and glycolysis in GBM cells, which was mediated by the IL-6/Stat3 pathway.