Integrating multi-omics approaches reveals metabolic reprogramming and identifies PDHX as a candidate node in triptolide-treated non-small Cell lung cancer

Introduction: Metabolic reprogramming is a central driver of malignant progression in non-small cell lung cancer (NSCLC). However, conventional targeted therapies face significant limitations due to drug resistance and narrow therapeutic windows. Triptolide, a natural tricyclic diterpenoid derived from Tripterygium wilfordii, exhibits potent antitumor activity, yet its precise mechanisms for modulating metabolic reprogramming in NSCLC remain elusive. Methods: efficacy was evaluated in xenograft models. Untargeted metabolomics identified metabolic alterations, while DARTS proteomics screened for potential TPL-interacting proteins. Results: HK2 degradation) and mitochondrial dysfunction. Conclusion: These findings suggest that TPL exerts antitumor effects in NSCLC by disrupting both glycolysis and mitochondrial function, with PDHX identified as a candidate mediator. Further studies are warranted to explore its therapeutic potential.