Fu-Zheng-Qu-Xie
(FZQX) decoction is a traditional Chinese
herbal
prescription for the treatment of lung cancer and exerts proapoptotic
and immunomodulatory effects. It has been clinically suggested to
be effective in improving the survival of postoperative early-stage
lung adenocarcinoma (LUAD), but the mechanism remains unclear. In
this study, we used network pharmacology coupled with metabolomics
approaches to explore the pharmacological action and effective mechanism
of FZQX against the recurrence and metastasis of postoperative early-stage
LUAD. Network pharmacology analysis showed that FZQX could prevent
the recurrence and metastasis of postoperative early-stage LUAD by
regulating a series of targets involving vascular endothelial growth
factor receptor 2, estrogen receptor 1, sarcoma gene, epidermal growth
factor receptor, and protein kinase B and by influencing the Ras,
PI3K-Akt, and mitogen-activated protein kinase signaling pathways.
In liquid chromatography–mass spectrometry analysis, 11 differentially
expressed metabolites, including PA(12:0/18:4(6Z,9Z,12Z,15Z)), PC(16:0/0:0)[U],
LysoPC(18:1(11Z)), and LysoPC(18:0), were discovered in the FZQX-treated
group compared to those in the model group before treatment or normal
group. They were enriched in cancer metabolism-related signaling pathways
such as central carbon metabolism in cancer, choline metabolism, and
glycerol phospholipid metabolism. Collectively, our results suggest
that the multicomponent and multitarget interaction network of FZQX
inhibits the recurrence and metastasis of postoperative early-stage
LUAD by activating the receptor signal transduction pathway to inhibit
proliferation, induce cell apoptosis, inhibit aerobic glycolysis,
and reprogram tumor lipid metabolism.