Objective To explore the mechanisms by which the Chinese medicine Cockroach improves the sensitivity of fluorouracil to dMMR colorectal cancer cells.Methods After selecting the mismatch repair gene-deficient colorectal cancer cells.The combined anti-tumor effects of these two drugs were assessed using the MTT method.The combination index was calculated based on the inhibition rate to determine the synergistic effect.The second-generation gene sequencing and lipid metabolism analysis were employed to identify differential metabolic genes,and database analysis was conducted to understand the pathways associated with differential genes.Results The cockroach was found to enhance the efficacy of 5-FU in HCT116 and DLD1 cells.GO functional enrichment analysis and KEGG analysis showed significant alterations in lipid metabolism,autophagy regulation,and apoptosis pathways.Further lipidomics analysis using LC/MS revealed statistically significant changes in a total of 153 lipid molecules,including lipids,sphingolipid metabolites,phospholipid metabolites,and glycerides.Conclusion The combination of cockroach and 5-FU demonstrates a synergistic enhancement of efficacy against dMMR colorectal cancer cells.This effect is likely achieved by modulating metabolic pathways,autophagy,and apoptosis mechanisms.It provides a theoretical basis for the clinical use of fluorouracil in the treatment of dMMR colorectal cancer patients.
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