Objective  To investigate the antitumor effect of Rumex chalepensis and its underlying molecular mechanism.

Methods  The inhibitory effect of Rumex chalepensis on the proliferation of four tumor cell lines (A549, AGS, HCT116, and HepG2) was detected using the MTT assay. After screening sensitive cell lines, flow cytometry combined with Annexin V-FITC/PI double staining was used to analyze cell cycle distribution and apoptosis. Based on network pharmacology, the active components and their corresponding targets were systematically screened. A drug-disease target network was constructed, and protein-protein interaction analysis was used to identify core targets. GO functional enrichment and KEGG pathway enrichment analyses were performed to predict the potential mechanisms of action.

Results  Rumex chalepensis had the strongest anti-proliferative effect on AGS gastric cancer cells, significantly inducing cell cycle arrest at the G2/M phase and promoting apoptosis. Network pharmacology analysis identified 10 active components and 216 common targets. Pathway analysis indicated that phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt), mitogen-activated protein kinase signaling pathway (MAPK), hypoxia-inducible factor-1 (HIF-1) and other signaling pathways might be involved in the regulatory process, among which the PI3K-Akt pathway might be the core regulatory pathway.

Conclusion  Rumex chalepensis inhibits the growth of AGS gastric cancer cells through multi-target synergistic effects, particularly by regulating the PI3K-Akt signaling pathway.

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