YinxingGujin decoction suppresses lung adenocarcinoma metastasis by modulating the TGF-β/STAT3/PD-L1 Axis: Network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE

Metastasis in lung cancer poses a significant clinical challenge. YinxingGujin Decoction (YXGJD), a traditional Chinese herbal formula with over 20 years of clinical application, has demonstrated remarkable efficacy in the treatment of lung cancer.

AIM OF THE STUDY

This study aimed to evaluate the inhibitory effects of YXGJD on lung adenocarcinoma (LUAD) metastasis and elucidate the underlying molecular mechanisms involved.

MATERIALS AND METHODS

UHPLC-Q-Exactive Orbitrap mass spectrometry was employed to comprehensively profile the major chemical constituents of YXGJD. A mouse model of LUAD metastasis was established by tail vein injection of A549 cells to assess the therapeutic potential and biosafety of YXGJD in vivo. Potential molecular targets and signaling pathways were identified through integrated network pharmacology analysis. The predicted mechanisms were validated experimentally via histopathological examination (H&E staining), Western blot, wound-healing assays, and siRNA-mediated gene silencing.

RESULTS

A total of 474 compounds were identified from YXGJD, primarily consisting of carbohydrates and glycosides, terpenoids, flavonoids, amino acids and peptides, and phenolic compounds. In vivo experiments demonstrate that YXGJD treatment significantly suppressed LUAD metastasis without inducing hepatic or renal toxicity. Network pharmacology analyses revealed that YXGJD inhibited epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) remodeling by disrupting the TGF-β/STAT3/PD-L1 signaling pathway. Furthermore, siRNA-mediated knockdown and wound-healing assays highlighted the novel role of PD-L1, beyond its function as an immune checkpoint molecule, in promoting LUAD cell migration.

CONCLUSION

This study systematically investigated the pharmacological efficacy and underlying mechanisms of YXGJD in the context of LUAD metastasis. Our findings strongly support the therapeutic potential of YXGJD as a promising clinical intervention for LUAD and provide a robust scientific foundation for further exploration into LUAD metastasis and YXGJD's mechanisms of action.