Ze-qi decoction inhibits neutrophil extracellular trap formation to suppress the progression and metastasis of non-small-cell lung cancer

Non-small cell lung cancer (NSCLC) research has been exploring complementary and well-established methods with clear mechanisms and less toxicity. Immune dysregulation is vital in the growth and metastasis of NSCLC. Although Ze-qi decoction (ZQD) exhibits therapeutic efficacy in patients with NSCLC, the specific mechanisms remain unclear. UPLC-HRMS was used to identify the primary chemical components. The potent molecular mechanisms were analyzed using network pharmacology and transcriptomic technology. The underlying molecular mechanisms were further investigated in vivo experiments. UPLC-HRMS revealed that 297 bioactive compounds were absorbed into the blood. Combined with the pharmacological analysis, liquiritigenin, vibsanin B, and 11-keto-beta-boswellic acid were revealed as potential active ingredients. Pharmacological analysis and transcriptomic profile indicated neutrophil extracellular trap (NET) formation as the anti-NSCLC target of ZQD. In vivo, ZQD hindered neutrophil recruitment and activation by decreasing hypoxia-inducible factor-1a, CD18, and Intercellular adhesion molecule-1 levels and suppressed NET formation, as evidenced by the downregulated biomarkers. These results were confirmed in the lung metastasis model. Overall design: RNA-seq of mouse substaneous tumor between control and high dose of ZQD treatment was applied at day 21 after ZQD treament.