Impact of tetrandrine on the malignant phenotype of glioma cells and its molecular mechanism

GUO Lingdi; MAO Xingyun; HENG Xueyuan; LI Ruiguo; WANG Hui; XU Ming

doi:10.13431/j.cnki.immunol.j.20260014

Abstract：Objective To investigate the effect of tetrandrine on the malignant phenotype of glioma cells and its molecular mechanism.Methods High-expression protein-coding genes potentially bound by tetrandrine in glioma were screened based on TCGA,GEO,MSigDB and CTD databases.The downstream pathways of transforming growth factor-β1(TGF-β1)were screened according to single-gene GSEA pathway analysis.CCK-8 assay was performed to determine cell viability,and crystal violet staining was used to measure colony-forming ability.Flow cytometry was applied to analyze cell cycle distribution and apoptosis rate,and wound-healing assay and Transwell assay were carried out to evaluate cell migration and invasion ability.RT-qPCR and Western blot were used to detect the expression of epithelial-mesenchymal transition(EMT)-related proteins and regulatory factors of the Smad2-Snail pathway.Cell models with high and low expression of TGF-β1 were constructed by transfection.Results TGF-β1 was highly expressed in the tumor tissues of glioma patients and was associated with poor prognosis.Tetrandrine could potentially bind to and inhibit TGF-β1 protein(P＜0.05).Tetrandrine significantly inhibited the proliferation,migration and invasion activities of glioma cells U251 and T98G,induced apoptosis,inhibited the EMT process and blocked the activation of the TGF-β1/Smad2-Snail pathway(P≤0.01).Down-regulation of TGF-β1 expression could inhibit the proliferation of glioma cells and induce apoptosis(P＜0.05,P＜0.01).Conclusion Tetrandrine inhibits the EMT process of glioma by regulating the TGF-β1/Smad2-Snail axis,providing a new theoretical basis for the treatment of glioma.