Investigating the Mechanism of Jiawei Weijin Decoction in Treating Non-Small Cell Lung Cancer Using Network Pharmacology, Bioinformatics Analysis and Experimental Validation.

Purpose: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide. While Qianjin Weijin Decoction is widely used in China for lung cancer treatment, Jiawei Qianjin Weijin Decoction (JWWJD), a modified version, has shown enhanced anti-metastatic effects. However, its active components and underlying mechanisms remain unclear. Methods: The effect of JWWJD against NSCLC was evaluated in vitro and in vivo, and the mechanisms were identified in combination with transcriptomics. Network pharmacology and bioinformatics were used to construct an anti-NSCLC prognostic model with JWWJD. The correlation between the expression of the prognostic gene and clinicopathological features was evaluated. The main active components of JWWJD were identified by LC-MS/MS and its anticancer effect and mechanism were investigated in vitro and in vivo. Results: JWWJD-containing serum significantly suppressed cell proliferation and migration, and induced apoptosis in NCI-A549 and NCI-H23 cells. Among different concentrations tested, 20% drug-containing serum showed the most potent inhibitory effect on NSCLC progression (all P-values < 0.05). In a BALB/c-nu mouse xenograft model, oral administration of high-dose JWWJD reduced tumor volume by 27.76% compared to control (P < 0.001). Transcriptomic analysis revealed that JWWJD treatment led to significant downregulation of SPP1 (Fold Change = 0.687, FDR < 0.05), a gene highly associated with poor prognosis in NSCLC patients. Using LC-MS/MS, curcumol was identified as the key active component in JWWJD. Molecular studies demonstrated that curcumol directly binds to SPP1 with strong affinity (KD = 4.55×10-6 M), downregulates its expression, and inhibits NSCLC cell migration and invasion. In vivo experiments showed that curcumol reduced tumor volume by 24.88% (P < 0.001). Conclusion: Our study, integrating transcriptomics, bioinformatics, LC-MS/MS, and experimental validation, revealed that JWWJD alleviates NSCLC metastasis by directly targeting SPP1. JWWJD and its active compound curcumol show promise as alternative therapies for NSCLC patients.