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

Abstract

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.

hsa_circ_0001610 knockdown modulates miR‐646‐STAT3 axis to suppress endometrial carcinoma progression

“…9,36,37 Moreover, STAT3 had a promoting effect on glycolysis in glioblastoma, bladder cancer, and oral squamous cell carcinoma. [38][39][40] Consistent with these reports, we also confirmed the oncogenic function of STAT3 in EC of promoting cell proliferation, migration, invasion, and glycolysis. Additionally, we identified that circ_0001610 could target STAT3 level through sponging miR-646.…”

Mechanism overview and target mining of atherosclerosis: Endothelial cell injury in atherosclerosis is regulated by glycolysis (Review)

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“…Ultimately, IFNs can activate members of the STAT family such as STAT1, STAT2, STAT3, STAT4, and STAT5, inducing expression of vital genes for tumorigenesis 27) . The products of JAK/STAT signaling pathway genes have been reported to be associated with glioma invasion, and many inhibitors have been evaluated for their utility in the treatment of GBM through in vitro and in vivo experiments involving blockade of this signaling pathway 13,16,20,22) . Previous studies revealed the antitumor effects of IFNs toward glioma, and the strong inhibitory effects of IFNs toward glioma invasion have been demonstrated in vitro 2,8,19) .…”