Paeoniflorin inhibits glioblastoma proliferation and promotes autophagy through the AKT/mTOR pathway.
Haima Li, Jia Ouyang, Yan Zhang, Zihao Zhang, Mingyang Sun, Ruen Liu, Chao Qian
Abstract
Open AccessPaeoniflorin (PF), one of the active components of Paeoniae radix, has antitumor activity in different cancers, including glioblastoma (GBM), which is mediated by its effect on autophagy. However, its underlying mechanism remains unclear. CCK-8, colony formation, scratch, and Transwell assays were performed to determine the effects of PF on GBM cell viability, proliferation, migration, and invasion. PI/RNase and Annexin V-FITC were used to detect cell cycle progression and apoptosis. Protein levels were detected by western blotting. The generation of autophagy flow in GBM cells was observed by transmission electron microscopy and LC3B-GFP plasmid transfection. PF induced autophagy and apoptosis in a dose-dependent manner in two human GBM cell lines (U87 and U118), inhibited cell proliferation, migration, and invasion, and caused cell cycle arrest. Further investigation of the mechanism underlying PF-mediated autophagy and inhibition of GBM cell growth showed that PF upregulated the autophagy-related proteins LC3B and P62 and downregulated P-AKT and P-mTOR, which may be involved in the regulation of autophagy. Treatment with an activator of AKT restored the expression of these proteins. The results indicate that PF induces autophagy and apoptosis through the AKT/mTOR pathway, suggesting its potential as a novel treatment for GBM.