The consumption of red meat, such as pork, beef, and lamb, has been associated with an incidence of gastric cancer (GC) due to certain processing and preparation methods. However, electromagnetic signal (EMS) exposure has demonstrated beneficial effects on food preparation, potentially improving food quality and reducing risk factors associated with GC. In our study, pork meat was treated with EMS, and this meat was investigated for its potential to reduce GC risk via in vitro and transcriptomic approaches. 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide and quantitative reverse transcription polymerase chain reaction assays were used to explore the cytotoxic and apoptotic effects of EMS-treated (EMS-T) and untreated (EMS-UT) pork meat extract on GC cells (KATO-III and S1M). The results indicated that KATO-III and S1M cells exhibited the highest inhibitory effect, with 32.8% and 24.53% inhibition, respectively, following treatment with 500 μg/mLEMS-T pork meat extract as compared to the EMS-UT meat extract treatment. Additionally, the apoptotic markers, CASP3 and CASP9, and the BAX/BCL2ratio suggested that apoptosis was initiated upon treatment with EMS-T pork meat extract. Transcriptomic analysis further revealed that EMS-T pork treatment led to 217 uniquely differentially expressed genes in KATO-III cells, with 135 suppressed genes and 82 stimulated genes. Notably, the mitogen-activated protein kinase (MAPK) pathway emerged as a notably interconnected signaling pathway, with key genes, such as DUSP5, MAP4K2, TGFB3, CACNA2D2, CD14, CACNA1H, and EREG, showing significant interactions. Specifically, EMS-T pork meat extract treatment resulted in the suppression of MAP4K2, TGFB3, and CD14, while DUSP5and CACNA2D2 were stimulated in KATO-III cells, contrasting with the gene expression profiles observed in cancer patients compared to healthy individuals according to The Cancer Genome Atlas data. Overall, these findings suggest that EMS-T meat may offer a novel approach for reducing GC risk by modulating apoptosis and the MAPK signaling pathway
