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

ABSTRACT: 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-1α, 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE304015 | GEO | 2026/02/25

REPOSITORIES: GEO

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Project description:Background Also the traditional Chinese medicine (TCM) theory of "Yang transforming into Qi with Yin constituting Form" was recognized as a potential mechanism underlying the tumorigenesis. The decoction based on this theory and the underlying molecular mechanisms remained exploration. Methods A TCM decoction was prepared based on "Yang transforming into Qi with Yin constituting Form". Its anti-tumorigenesis effect was evaluated on mouse models of hepatocellular carcinoma (HCC) (H-rasG12V transgenic mice (Ras-Tg) and Diethylnitrosamine (DEN)-induced HCC mice) by liver/body weight, number and size of tumors, histopathological changes and serum biochemistry. RNA sequencing was utilized to check differentially expressed genes (DEGs) and gene ontology (GO) and KEGG were used for bioinformatics analysis. The concerned biological processes were further confirmed by RT-qPCR and metabolite detection kits. Results The TCM decoction significantly suppressed both Ras oncogene- and DEN-induced hepatic tumorigenesis evidenced by reduced serum ALT and AST levels, liver weight, liver/body weight ratio, hepatic tumor numbers and sizes. RNA sequencing showed 659 up-regulated genes and 222 down-regulated genes in comparison of liver tissues between TCM-treated and untreated Rag-Tg (n=5). GO entries and KEGG analysis revealed multiple biological processes and pathways involving the hepatic tumorigenesis suppressing effective of the TCM. Further molecular examination confirmed that activation of retinal metabolism, reduction of ROS and electrophilic levels by inhibiting the H2O2 production and promoting GSH production, and inhibition of expression of inflammation factors play pivotal roles in the anti-tumorigenesis effects of TCM. Conclusion A TCM decoction based on "Yang transforming into Qi with Yin constituting Form" showed effective anti-hepatic tumorigenesis functions and its regulation functions on retinal, ROS and inflammation processes play important roles. The present study provides valuable clue for clinical therapy on tumorigenesis.

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

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