Polyphyllin I(MUST)

Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive and heterogeneous hematological malignancy of B-cell origin, commonly observe in clinical practice. Chemotherapy resistance poses a significant challenge to DLBCL treatment, necessitating novel therapies. Polyphyllin I (PPI) exhibits anticancer effects on various cancer cells, but its impact on DLBCL remains unclear. This study investigated the mechanism underlying PPI in treating DLBCL, specifically focusing on the caspase-6/ZBP1/NLRP3 pathway involved in pyroptosis and apoptosis. The role caspase-6 plays in regulating pyroptosis is unknown. We hypothesized PPI activates this pathway, triggering tumor cell death. Through both in vitro and in vivo experiments, we found that PPI significantly promoted DLBCL cell pyroptosis and apoptosis by activating the caspase-6/ZBP1/NLRP3 pathway. These findings suggest that the caspase-6 pathway has the potential to be developed as a novel treatment for DLBCL. Further research is needed to explore the clinical application of PPI in lymphoma treatment and its potential synergies with other drugs.

Lung cancer is a significant hazard to human health, with limited treatment options. Although CDK4/6 inhibitors like Palbociclib (Palb) have shown clinical promise, their effectiveness is often compromised by resistance. Our findings indicate that the Palb may promote M2-like macrophage polarization, which can facilitate tumor progression through immunosuppression. This study investigates the effect of Polyphyllin I (PPI) in counteracting Palb-induced M2 macrophage polarization and explored its synergistic anti-tumor potential when combined with Palb. In vitro, a macrophage polarization model showed that Palb enhanced the expression of M2 macrophage markers, which could be reversed by PPI. LLC cells were cultured with macrophage-conditioned medium (CM) showed that the PPI and Palb combination-CM group exhibited decreased proliferation, migration, and invasion capabilities in LLC cells and inhibited epithelial-mesenchymal transition (EMT) compared to the Palb-CM group. Moreover, the combination of PPI and Palb also enhanced anti-tumor effect in vivo. Mechanistically, the JAK-STAT pathway was enriched, and key signaling proteins associated with macrophage polarization, including TWEAK, p-JAK1 and p-STAT1, were significantly upregulated in the PPI-treated group. PPI can reverse Palb-induced M2 polarization by activating the TWEAK/JAK1/STAT1 signaling pathway, which can enhance the anti-tumor efficacy of Palb. These findings support PPI as a potential adjunct to CDK4/6 inhibitors for lung cancer therapy.