Abstract Objective: This study investigates the effects of Celastrus orbiculatus Thunb extract (COE) on the metastasis of gastric cancer (GC) through MED12, aiming to elucidate the underlying mechanisms. Materials and Methods: Cell viability was evaluated via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Adhesion and transwell assays were conducted to assess the adhesion, invasion, and migration capabilities of mediator complex subunit 12 (MED12)-deficient GC cells. Cell movement was tracked using the high-content imaging system. Western blotting was employed to examine the impact of COE on the expression of MED12 and the alterations in proteins related to invasion and migration in GC cells. Results: COE reduces MED12 expression in GC cells through a distinct mechanism. Experimental data demonstrate that COE and direct modulation of MED12 expression significantly impair the infiltration and movement of GC cells, with a notable reduction in movement distance. Furthermore, both treatments substantially downregulate matrix metalloproteinases expression, thereby inhibiting the invasive potential of tumor cells. In addition, COE treatment and MED12 deficiency reverse epithelial-mesenchymal transition-related protein alterations, providing new insights into the mechanisms driving tumor metastasis. Conclusions: MED12 deficiency serves as a critical barrier to GC invasion and metastasis, while COE modulation of MED12 expression offers a promising strategy for inhibiting GC progression. These results not only suggest new therapeutic strategies for GC but also propose possible routes for the creation of anti-tumor drugs.
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