Transcriptome analysis displays new molecular insights into the mechanisms of action of Mebendazole in gastric cancer cells

Abstract

Gastric cancer (GC) is a common cancer worldwide. Therefore, searching for effective treatments is essential, and drug repositioning can be a promising strategy to find new potential drugs for GC therapy. For the first time, we sought to identify molecular alterations and validate new mechanisms related to Mebendazole (MBZ) treatment in GC cells through transcriptome analysis using microarray technology. Data revealed 1066 differentially expressed genes (DEGs), of which 345 (2.41 %) genes were upregulated, 721 (5.04 %) genes were downregulated, and 13,231 (92.54 %) genes remained unaltered after MBZ exposure. The overexpressed genes identified were CCL2, IL1A, and CDKN1A. In contrast, the H3C7, H3C11, and H1-5 were the top 3 underexpressed genes. Gene set enrichment analysis (GSEA) identified 8 pathways significantly overexpressed in the treated group (p < 0.05 and FDR<0.25). The validation of the expression of top desregulated genes by RT-qPCR confirmed the transcriptome results, where MBZ increased the CCL2, IL1A, and CDKN1A and reduced the H3C7, H3C11, and H1-5 transcript levels. Expression analysis in samples from TCGA databases correlated that the lower ILI1A and higher H3C11 and H1-5 gene expression are associated with decreased overall survival rates in patients with GC, indicating that MBZ treatment can improve the prognosis of patients. Thus, the data demonstrated that the drug MBZ alters the transcriptome of the AGP-01 lineage, mainly modulating the expression of histone proteins and inflammatory cytokines, indicating a possible epigenetic and immunological effect on tumor cells, these findings highlight new mechanisms of action related to MBZ treatment. Additional studies are still needed to better clarify the epigenetic and immune mechanism of MBZ in the therapy of GC.