Schisandrin C inhibits AKT1-regulated cell proliferation in A549 cells

Lung cancer is the leading cause of cancer-related mortality. Cancer poses a significant challenge to human health and remains a persistent and pressing issue. Schisandrin C is one of the active ingredients of Schisandra chinensis and has various biological and pharmacological activities. This study aimed to investigate the effects of Schisandrin C on lung cancer and the underlying mechanism involved.

A network pharmacology strategy was used to screen the target genes and pathways involved in the relationship between Schisandrin and lung cancer. Next, a single-cell RNA sequencing (scRNA-seq) assay revealed the expression of genes specifically expressed in lung cancer epithelial cells. A549 cells were subsequently treated with Schisandrin C for 24 h or 48 h, cell viability was assessed via MTT and EdU staining experiments, and target gene expression was measured via RT-qPCR and immunofluorescence assays. Moreover, lung cancer patient tissues were observed via multiplex immunofluroscence staining.

AKT1, CA9, BRAF, EGFR, ERBB2 and PIK3CA were overlapping target genes for network pharmacology and the scRNA-seq strategy. In vitro, the RT-qPCR results indicated that Schisandrin C inhibited the mRNA expression of the AKT1, CA9, FASN, MMP1, EGFR and BRAF genes. In clinical samples from patients with lung cancer, the expression levels of CA9 and AKT1 were found to be significantly higher in lung tumor tissues than in the adjacent normal (TAN) tissues. Moreover, the administration of an AKT kinase inhibitor reversed the inhibitory effect of Schisandrin C on A549 cells proliferation, whereas the administration of a CA9 inhibitor failed to have a similar effect.

Schisandrin C effectively suppressed the proliferation and viability of A549 cells. Its mechanism was related to the inhibition of the AKT1 signaling pathway.