Brexpiprazole regulates EMT and metastasis through inhibition of SREBP1/SNAI1 signalling pathway in colorectal cancer cells

Abstract

Abstract Objective: To investigate the role and mechanism of SREBP1/SNAI1 signalling pathway in the effect of brexpiprazole on EMT and metastasis of CRC. Methods:The effects of different concentrations of brexpiprazole on the migration and invasion in vitro as well as the expression of proteins are were examined by cell scratch, Transwell, Western blot, ELISA, immunofluorescence, dual luciferase promoter assay, transmission electron microscopy. A metastatic model of CRC in nude mice was established, Western blot,HE staining, and PET/CT were utilized to explore the effects of brexpiprazole on lung metastasis of CRC. Results:Brexpiprazole significantly inhibited the migration and invasion of CRC , down-regulated the expression levels of SREBP1(m), Snail and MMP9 , up-regulated E-Cad and ZO1 and decreased the secretion levels of ICAM-1 and VEGF in the supernatant of CRC.Western blot and dual luciferase assays showed that SREBP1 could directly govern on the expression level of SANI1. In vivo experiments, on the other hand, showed that brexpiprazole significantly inhibited the formation of CRC lung metastases, suppressed the expression of SREBP1(m), Snail and MMP9, and up-regulated the expression of E-Cad and ZO1. Conclusion:Brexpiprazole inhibited migration, invasion and metastasis of CRC by inhibiting the SREBP1/SNAI1 signalling pathway and down-regulating the expression of EMT-related factors.