In the present study, we investigate the effect of brexpiprazole on cholesterol metabolism in colorectal cancer and its possible mechanism by transcriptome analysis andvalidation. Cell Counting Kit-8 (CCK-8) was used to detect the effect of brexpiprazole on the viability of colorectal cancer cells. Then, differential genes were identified by RNA-seq assay after treating colon cancer cells (HCT-116) with or without 20.0 μmol/L brexpiprazole for 24 h. After that, PPI network were constructed by the STRING database and Cytoscape to identify the top 120 hub genes, and then GO and KEGG enrichment analysis were measured. Differentially expressed protein and gene were measured by western blot and q-PCR, respectively. Finally, the mechanism of brexpiprazole regulating cholesterol metabolism in colorectal cancer was revealed through a series of in vitro and vivo experiments. The results of WB and q-PCR revealed that brexpiprazole significantly reduced the expression of HMGCR and HMGCS1. Besides, remarkable reduction of cellular Total Cholestenone (TC) levels in HCT-116 and SW620 cells after brexpiprazole treatment. Moreover, brexpiprazole also resulted in the restrained expression of p-PI3K, p-AKT, and SREBP2 in vivo and vitro.
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