Paris saponin VII restrains PD-L1 mediated immune evasion through the AKT1 and STAT3 signaling pathways

Glioblastoma (GBM) represents a highly aggressive and fatal type of brain cancer. Paris saponin VII (PS VII) is noteworthy for its potential anti-tumor properties, yet the anti-tumor effect and underlying mechanism of PS VII on GBM remain unclear. This study demonstrated that PS VII inhibited the proliferation and migration rates of GBM cells. PS VII induced cell cycle arrest at the G2/M phase, which was linked to significant reductions in the expression of CDK1, Cyclin D1 and CDK2. Furthermore, PS VII triggered cells apoptosis in a dose-dependent manner by up-regulating the expression of Bax while down-regulating that of Bcl-2, leading to the activation of Caspase-3 and PARP. Further investigation revealed that PS VII effectively suppressed the expression of PD-L1, a key factor in the development of tumors. Additionally, PS VII decreased PD-L1 expression by modulating the activities of AKT1 and STAT3 signaling pathways. In tumor/T cells co-culture system, PS VII restored the activation of T cells by inhibiting PD-L1 expression. Notably, PS VII inhibited GBM cells proliferation, migration by reducing PD-L1. In vivo study showed that PS VII reduced the volume and size of tumors, and achieved better therapeutic effects at higher concentrations. These results revealed PS VII's previously unrecognized anti-tumor effects on GBM, suggesting its potential as a therapeutic drug for GBM treatment.