Toosendanin Induces Lung Squamous Cell Carcinoma Cell Apoptosis and Inhibits Tumor Progression via the BNIP3/AMPK Signaling Pathway

Abstract

AbstractLung squamous cell carcinoma (LUSC) is the second most common type of non‐small cell lung cancer. Toosendanin can target critical cancer cell survival and proliferation. However, the function of toosendanin in LUSC is limited. Cancer cell proliferative capacity is detected using cell morphology, colony formation, and flow cytometry. The invasiveness of the cells is detected by a Transwell assay, western blotting, and RT‐qPCR. Nude mice are injected with H226 (1×106) and received an intraperitoneal injection of toosendanin every 2 days for 21 days. RNA sequence transcriptome analysis is performed on toosendanin‐treated cells to identify target genes and signaling pathways. With increasing concentrations of toosendanin, the rate of cell proliferation decreases and apoptotic cells increases. The number of migrated cells significantly reduces and epithelial‐mesenchymal transition is reversed. Injection of toosendanin in nude mice leads to a reduction in tumor volume, weight, and the number of metastatic tumors. Furthermore, KEGG shows that genes related to the AMPK pathway are highly enriched. BNIP3 is the most differentially expressed gene, and its expression along with phosphorylated‐AMPK significantly increases in toosendanin‐treated cells. Toosendanin exerts anticancer effects, induces apoptosis in LUSC cells, and inhibits tumor progression via the BNIP3/AMPK signaling pathway.