The interplay between glioblastoma and microglia cells leads to endothelial cell monolayer dysfunction via the interleukin-6-induced JAK2/STAT3 pathway.
Neutralizing antibody against BTC abrogated activation of both EGFR and NF-ᴋB in response to inhibition of STAT3; with combinatorial blockade of STAT3 and BTC inducing apoptosis in glioblastoma cells.
Signal transducer and activator of transcription 3 (Stat3) is a key signaling protein driving major hallmarks of cancer and represents a promising target for the development of targeted glioblastoma therapies.
On multivariate analyses with the COX proportional hazards regression model including pY705-Stat3 expression, age and relapse status, pY705-Stat3 status was an independent prognostic factor in glioblastoma (P < 0.001).
According to the results of both in vitro and in vivo assays, a combined therapy of LV‑STAT3 siRNA with AZD0530 could enhance therapeutic effects on glioblastoma, supporting the idea that the combination of LV‑STAT3 siRNA and AZD0530 could serve as a novel and effective strategy to combat glioblastoma.
Evidences from both preclinical and clinical studies have demonstrated that STAT3 plays a critical role in several malignancies associated with poor prognosis such as glioblastoma and triple-negative breast cancer, and STAT3 inhibitors have shown efficacy in inhibiting cancer growth and metastasis.
Western blot analysis revealed elevated SHP-1 expression and reduced phosphorylated (p)-STAT3 expression in glioblastoma cells treated with VB compared with controls.
These results demonstrate that the regulation of Jmjd3 by STAT3 maintains repression of differentiation specific genes and is therefore important for the maintenance of self-renewal of normal neural and glioblastoma stem cells.