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Histone demethylase KDM6B inhibitor GSK-J4 sensitizes glioma cells to tyrosine kinase inhibitor anlotinib in vitro by reducing PDGFRA expression

Year: 2026

Type: article

Abstract: This study investigated the pharmacological effects and potential mechanisms of the tyrosine kinase inhibitor anlotinib and the histone lysine demethylase 6B (KDM6B) inhibitor GSK-J4 on glioma cells. Brain pathological samples were analyzed with immunohistochemistry. The glioma cells U87MG and U251, and brain endothelial cell hCMEC/D3 were used in this study. Cell proliferation and migration were determined with CCK8 and scratch assays. The mRNA expressions of platelet derived growth factor receptor alpha ( PDGFRA ), PDGFR beta ( PDGFRB ) and KDM6B were detected with RT-qPCR. The protein levels of total PDGFRA and phosphorylated PDGFRA (p-PDGFRA) were measured with western blotting. The protein levels of total PDGFRA, p-PDGFRA and KDM6B were significantly elevated in malignant glioma tissues relative to control brain tissues. In vitro experiments demonstrated that anlotinib effectively inhibited glioma cell proliferation and migration, while GSK-J4 increased its inhibitory activity. The combination of two inhibitors showed no additional cytotoxicity toward brain endothelial cells. Further studies elucidated that the anlotinib primarily functions as a PDGFRA kinase inhibitor, whereas GSK-J4 exerts its effects through transcriptional repression of PDGFRA gene expression. The combination of anlotinib and GSK-J4 achieves dual inhibition of PDGFRA at both transcriptional and post-translational levels, representing a promising therapeutic strategy for glioma patients.

Source: Advances in Cancer Biology - Metastasis

DOI: 10.1016/j.adcanc.2026.100171

Authors: Biaogang Han, Juan Li, Li Li, Yongqing Shen, Xiaoqiang Guo, Aixia Sui