Paeoniflorin inhibits human glioma cells via STAT3 degradation by the ubiquitin-proteasome pathway.

摘要: We investigated the underlying mechanism for potent proapoptotic effect of paeoniflorin (PF) on human glioma cells in vitro, focusing signal transducer and activator transcription 3 (STAT3) signaling. Significant time- dose-dependent apoptosis inhibition proliferation were observed PF-treated U87 U251 cells. Expression STAT3, its active form phosphorylated STAT3 (p-STAT3), several downstream molecules, including HIAP, Bcl-2, cyclin D1, Survivin, significantly downregulated upon PF treatment. Overexpression induced resistance to PF, suggesting that was a critical target PF. Interestingly, rapid downregulation consistent with accelerated degradation, but not dephosphorylation or transcriptional modulation. Using specific inhibitors, we demonstrated prodegradation mainly through ubiquitin–proteasome pathway rather than via lysosomal degradation. These findings indicated PF-induced growth suppression proteasome-dependent degradation STAT3.