Lidocaine Inhibits the Proliferation of Non-Small Cell Lung Cancer and Exerts Anti-Inflammatory Effects Through the TLR-9/MyD88/NF-κB Pathway.

Abstract

Lung cancer represents a significant global health burden, with non-small cell lung cancer (NSCLC) being the most common subtype. The current standard of care for NSCLC has limited efficacy, highlighting the necessity for innovative treatment options. Lidocaine, traditionally recognized as a local anesthetic, has emerged as a compound with potential antitumor and anti-inflammatory capabilities. This study was designed to explore the impact of lidocaine on NSCLC cell proliferation and inflammation, particularly focusing on the Toll-like receptor 9 (TLR)-9/MyD88/NF-κB signaling pathway. A nude mice model of NSCLC was employed, with animals receiving lidocaine at different concentrations. In vitro experiments on A549 cells involved exposure to lidocaine, followed by assessment of cell viability, cytokine expression, and TLR-9 levels using the 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay, enzyme-linked immunosorbent assay, and Quantitative Real-time polymerase chain reaction (qPCR). Protein levels were evaluated via Western blot analysis. Additionally, A549 cells were transfected with a TLR-9-overexpressing lentivirus to dissect the role of TLR-9 in lidocaine's mechanism of action. Treatment with lidocaine led to a significant reduction in tumor dimensions and a decrease in inflammatory marker expression in the NSCLC mouse model. In cellular assays, lidocaine effectively suppressed A549 cell proliferation and the expression of inflammatory cytokines. The overexpression of TLR-9 partially negated the suppressive effects of lidocaine, underscoring the significance of the TLR-9/MyD88/NF-κB pathway in mediating lidocaine's effects. Lidocaine's inhibitory effects on NSCLC cell proliferation and its anti-inflammatory mechanisms are mediated through the TLR-9/MyD88/NF-κB pathway. The study's results offer promising insights into the therapeutic potential of lidocaine in NSCLC and pave the way for future investigations into its application in cancer therapy.