Schisandrin B inhibits epithelial-mesenchymal transition and stemness of large-cell lung cancer cells and tumorigenesis in xenografts via inhibiting the NF-κB and p38 MAPK signaling pathways

Lung cancer is one of the most common types of cancer in the world, resulting in numerous cancer-associated deaths. The properties of cancer stem cells (CSCs) are important for the initiation and deterioration of lung cancer. Schisandrin B (SchB), an active compound extracted from Schisandra chinensis, exerts anticancer effects in various malignancies, including lung cancer. Nevertheless, the potential of SchB in epithelial-mesenchymal transition (EMT) and CSC features of large-cell lung cancer remains unclear. The present study established cancer stem-like cells derived from large-cell lung cancer cells, NCI-H460 and H661, and revealed that SchB inhibited the viability of cancer stem-like cells at concentrations of ≥40 µmol/l. Moreover, SchB prominently inhibited cell migration, invasion and EMT. Sphere-forming assays and western blotting demonstrated that the stemness of cancer stem-like cells was alleviated by SchB treatment. Mechanistically, the current findings revealed that SchB contributed to the suppression of the NF-κB and p38 MAPK signaling pathways. Notably, further results revealed that the malignant behaviors of NCI-H460-CSCs induced by the activation of the NF-κB and p38 MAPK signaling pathways were suppressed by SchB treatment. Consistently, the inhibitory role of SchB in EMT and CSC activities, as well as in the activation of the NF-κB and p38 MAPK signaling pathways, was confirmed in vivo. In conclusion, the present study demonstrated that SchB exerted inhibitory effects on large-cell lung cancer cells via targeting the NF-κB and p38 MAPK signaling pathways, suggesting that SchB may act as a potential therapeutic drug for large-cell lung cancer.