Mechanism of Morin in Inhibiting Gastric Cancer Cells via Regulation of the PI3K/Akt Pathway
This study integrates network pharmacology, molecular docking, and in vitro experiments to elucidate the anti-gastric cancer mechanism of morin, an active flavonoid from Mori Ramulus. Network analysis identified 178 potential targets of Mori Ramulus and 13,100 gastric cancer-related targets, with 159 intersecting targets. Enrichment analysis highlighted the PI3K/Akt pathway as a key mediator. Molecular docking and dynamics simulations confirmed stable binding between morin and PIK3R1, which is significantly overexpressed in gastric cancer tissues. In vitro, morin (100–400 μmol/L) dose-dependently inhibited AGS cell proliferation, induced G0/G1 phase arrest, and promoted apoptosis (P<0.05, 0.01). Western blotting revealed downregulation of PI3K/Akt pathway proteins (p85α, p110β, p-Akt) and cell cycle-related proteins (Bcl-2, CCND1, CDK4, CDK6), alongside upregulation of Bax and p21 (P<0.05, 0.01). Co-treatment with the PI3K agonist 740Y-P significantly reversed these effects (P<0.05, 0.01), confirming pathway dependence. These findings demonstrate that morin targets PIK3R1 to suppress PI3K/Akt signaling, thereby inhibiting proliferation and inducing apoptosis and cell cycle arrest in gastric cancer cells. The study underscores morin's potential as a natural, multi-target lead compound with low toxicity, though further validation in additional cell lines and gene-level manipulations is warranted.