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 mu mol/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-kappa B and p38 MAPK signaling pathways. Notably, further results revealed that the malignant behaviors of NCI-H460-CSCs induced by the activation of the NF-kappa B 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-kappa B 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-kappa B and p38 MAPK signaling pathways, suggesting that SchB may act as a potential therapeutic drug for large-cell lung cancer.

Automated summary

Schisandrin B (SchB) shows inhibitory effects on cancer stem-like cells derived from large-cell lung cancer cells by targeting the NF-kappa B and p38 MAPK signaling pathways, leading to reduced stemness, migration, and invasion capabilities of the cells. SchB treatment suppresses the malignant behaviors induced by these signaling pathways in vivo, suggesting its potential as a therapeutic drug for large-cell lung cancer.