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<div><p>Background</p><p>Colorectal cancer (CRC) is a significant disease worldwide, with high mortality rates. Conventional treatment methods often lead to metastasis and drug resistance, highlighting the need to explore new drugs and their potential molecular mechanisms. In this study, we investigated the effects of arctigenin on CRC cell proliferation, migration, invasion, apoptosis, and related protein expression, as well as its potential molecular mechanisms.</p><p>Methods</p><p>The CCK-8 assay, transwell migration and invasion assays, flow cytometry, immunoblotting and immunofluorescence staining, western blot and an allograft tumor transplantation model was used.</p><p>Results</p><p>Our study revealed that arctigenin effectively inhibited CRC cell proliferation, migration, and invasion in a dose-dependent manner, while also inducing apoptosis. At the molecular level, arctigenin significantly downregulated the expressions of PCNA, Bcl2, MMP-2, and MMP-9 and upregulated the expressions of Bax and cleaved caspase-3. Additionally, arctigenin demonstrated the ability to inhibit the epithelial-mesenchymal transition (EMT) process by upregulating E-cadherin and downregulating mesenchymal markers, such as N-cadherin, Vimentin, Snail, and Slug. Furthermore, arctigenin could inhibit the activation of the PI3K-AKT-mTOR signaling pathway, which has been implicated in cancer progression. In vivo experiments also showed that arctigenin significantly reduced tumor volume and size compared to the control group, with no significant adverse effects on the liver.</p><p>Conclusions</p><p>This is the first study to elucidate the mechanism by which arctigenin inhibits colorectal cancer metastasis through the PI3K-AKT-mTOR signaling pathway by suppressing the EMT process at the molecular level.</p></div>