Matrine inhibits the malignant behaviors of nasopharyngeal cancer cells by directly targeting CTSL

Nasopharyngeal cancer (NPC) is a highly heterogeneous malignant tumor that originates in the top and lateral walls of the nasopharyngeal cavity. Matrine is a natural alkaloid with diverse pharmacological activities and exhibits antitumor effects. The primary objective of this study is to investigate the effects and the underlying mechanisms of matrine on NPC. Cell proliferation was evaluated through both the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the colony formation assay. Cell apoptosis was detected by flow cytometry and the TdT-mediated dUTP nick end labeling (TUNEL) assay. The release level of lactate dehydrogenase (LDH) was detected using a specific kit. The invasive and migratory capabilities of the cells were assessed using the transwell assay and the wound healing assay, respectively. The tube formation capability of the cells was assessed using the tube formation assay. Potential targets for matrine in the treatment of NPC were predicted using network pharmacology and molecular docking. The expression levels of the hub genes within NPC were analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) database. The gene expression levels were detected using western blot. Then, the mouse xenograft model was constructed to conduct in vivo validation experiments, and immunohistochemistry (IHC) technology was employed to detect the expression of CTSL, matrix metalloproteinase 2 (MMP2), and matrix metalloproteinase 9 (MMP9) in mouse NPC tumor tissues. Matrine exhibited inhibitory effects on NPC cell proliferation, migration, invasion, and HUVEC tube formation while simultaneously promoting cell apoptosis. Cathepsin L (CTSL) was identified as a potential target for matrine in the treatment of NPC. The knockdown of CTSL suppressed the malignant behaviors of NPC cells. The overexpression of CTSL counteracted the inhibitory effects of matrine on the malignant behaviors of NPC cells. Matrine halts the progression of NPC cells towards malignancy by specifically targeting CTSL. It offers a fresh perspective on the application of matrine in the targeted therapy for NPC.