Glioma is a malignant tumor that affects all kinds of people all over the world. It demonstrates remarkable infiltrative and invasive features. The high expression of interleukin-13 receptor subunit alpha-2 (IL-13Rα2) reportedly plays a pivotal role in some cancers. However, whether IL-13Rα2 contributes to glioma remains unknown. This study demonstrates that IL-13Rα2 is significantly up-regulated in human glioma tissue samples. It is also associated with late stages of disease progression and diminished survival in glioma patients. Gain- and loss-of-function studies demonstrate that IL-13Rα2 promotes the growth, migration, and invasion of glioma cells. In addition, mechanistic investigations show that IL-13Rα2 activates Scr, phosphatidylinositol 3 kinase (PI3K), Akt, and mTOR. Also, restraining Scr in glioma cells attenuates the activation of Scr/PI3K/Akt/mTOR pathway by IL-13Rα2, whereas the silencing of Scr markedly rescues the pro-invasive effect of IL-13Rα2. In conclusion, our results suggest that the high expression of IL-13Rα2 is significantly associated with the growth and metastasis of human glioma cells via the Scr/PI3K/Akt/mTOR pathway, while IL-13Rα2 may be a potential therapeutic target for glioma treatment.

The occurrence of an inherent or acquired resistance to temozolomide (TMZ) is a major burden for patients suffering from glioma. Recently, studies have demonstrated that microRNAs play an important role in the regulation of tumor properties in cancers. However, whether miR‐497 contributes to glioma resistance to chemotherapy is not fully understood. In this study, we showed that the expression of miR‐497 was markedly up‐regulated in TMZ‐resistant glioma cells; high miR‐497 expression level was associated with TMZ‐resistant phenotype of glioma cells. The down‐regulation of miR‐497 in glioma cells enhanced the apoptosis‐induction and growth inhibition effects of TMZ both in vitro and in vivo, whereas promotion of miR‐497 increased the chemosensitization of glioma cells to TMZ. The increased level of miR‐497 in TMZ‐resistant glioma cells was concurrent with the up‐regulation of insulin‐like growth factor 1 receptor (IGF1R)/insulin receptor substrate 1 (IRS1) pathway‐related proteins, that is, IGF1R, IRS1, mammalian target of rapamycin (mTOR), and Bcl‐2. In addition, the knockdown of mTOR and Bcl‐2 reduced the tolerance of glioma cells to TMZ. Our results demonstrated that overexpression of miR‐497 is significantly correlated with TMZ resistance in glioma cells by regulating the IGF1R/IRS1 pathway. Therefore, miR‐497 may be used as a new target for treatment of chemotherapy‐resistant glioma.

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Brusatol (Bru), a Chinese herbal extract, has a variety of anti-tumor effects. However, little is known regarding its role and underlying mechanism in glioblastoma cells. Here, we found that Bru could inhibit the proliferation of glioblastoma cells in vivo and in vitro. Besides, it also had an inhibitory effect on human primary glioblastoma cells. RNA-seq analysis indicated that Bru possibly achieved these effects through inhibiting the expression of extracellular matrix protein 1 (ECM1). Down-regulating the expression of ECM1 via transfecting siRNA could weaken the proliferation and invasion of glioblastoma cells and promote the inhibitory effect of Bru treatment. Lentivirus-mediated overexpression of ECM1 could effectively reverse this weakening effect. Our findings indicated that Bru could inhibit the proliferation and invasion of glioblastoma cells by suppressing the expression of ECM1, and Bru might be a novel effective anticancer drug for glioblastoma cells.

These results indicated that the angiogenic effects of A549 CM are largely mediated through activation of the PI3K-Akt in endothelial cells, and that the Akt1 is crucial in this process, which may provide a therapeutic target for decreasing tumor angiogenesis.