Abstract: OBJECTIVE： To explore whether glycyrrhizic acid has an anti-lung adenocarcinoma effect and its mechanism in vitro. METHODS： Human lung adenocarcinoma cells A549，NCI-H1299，normal human lung epithelial cells Beas-2b，and human umbilical vein endothelial cells (HUVECs) were treated with glycyrrhizic acid at concentrations of 0.5-6 mmol/L for 48 hours. The MTT assay was used to detect effects on growth and viability. Flow cytometry was used to assess effects on cell cycle and apoptosis in A549 cells，comparing the untreated with cells treated with 4 mmol/L glycyrrhizic acid. Network pharmacology was employed to predict key targets and pathways impacted by glycyrrhizic acid. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to verify key targets after treatment with 4 mmol/L glycyrrhizic acid in A549 cells. RESULTS： At concentrations of 1-6 mmol/L，glycyrrhizic acid significantly inhibited the viability of A549 and NCI-H1299 cells，while showing a weaker inhibitory effect on normal lung epithelial cells Beas-2b and HUVECs. After treatment with 4 mmol/L glycyrrhizic acid，the proportion of apoptotic cells in the control group was (3.73±1.43)%，compared to (44.41±10.28)% in the treatment group. The proportion of cells in the G₀/G₁ phase in the control group was (45.7±0.98)%，while the treatment group had (53.03±2.25)%. Network pharmacology predicted the key targets were caspase 3，STAT3，SRC，MMP9，and PTGS2，which are involved in apoptosis，cell cycle arrest，and oxidative stress signaling pathways. In addition，glycyrrhizic acid significantly reduced the mRNA expression of SRC and PTGS2 in A549 cells，inhibited the expression of p-STAT3，and activated the cleavage of caspase 3. CONCLUSION： Our in vitro studies indicate that glycyrrhizic acid selectively killed human lung adenocarcinoma cells A549，primarily through the induction of cell cycle arrest and apoptosis，possibly involving downregulation of SRC，PTGS2，and p-STAT3 expression levels and activation of caspase 3.

Key words: glycyrrhizic acid, lung adenocarcinoma, cell apoptosis, cell cycle arrest, key targets, caspase 3