High-salt diet promote colorectal cancer progression by inhibiting necroptosis via SGK1

Introduction : The purpose of this study was to explore the potential mechanism of high salt diet on the progression of colorectal cancer. Methods : Colorectal cancer cells Caco-2 and HT-29 were treated with varying concentrations of sodium chloride. Flow cytometry was used to assess apoptosis in each group, wound healing assays were employed to evaluate cell migration, and Transwell assays were conducted to measure cell invasion. The expression levels of SGK1 in each group were analyzed using qRT-PCR and WB. Subsequently, SGK1 interfering vectors were constructed and transfected into the cells, and their effects on apoptosis, migration, invasion, and the expression of necroptosis-related proteins in colorectal cancer cells were investigated. Finally, the impact of a high-salt diet on tumor growth was examined by analyzing tumor formation in nude mice. Results : High-dose sodium chloride exposure significantly enhances the migration and invasion capabilities of Caco-2 and HT-29 cells while upregulating the expression of SGK1. Introducing an SGK1 interference vector effectively attenuates the sodium chloride-induced increase in migration and invasion abilities of colorectal cancer cells and promotes necroptosis in these cells. In vivo experiments in mice demonstrate that a high-salt diet accelerates the progression of colorectal cancer, whereas treatment with SGK1 inhibitors suppresses tumor growth in mouse models. Conclusion : High-salt diet can enhance the malignant biological behavior of colorectal cancer cells and promote in vivo colorectal cancer growth by upregulating SGK1 expression.