Ciprofol Suppresses Glycolysis and Epithelial-Mesenchymal Transition (EMT) in Colorectal Cancer Cells by Activating Adenomatous Polyposis Coli to Modulate the Wnt/β- catenin Signaling Pathway

Abstract

Abstract Propofol, frequently employed as a perioperative anesthetic for patients with colorectal cancer, has been documented to demonstrate anticancer properties. Ciprofol, an innovative anesthetic derived from propofol, showcases unexplored impacts on the viability of colorectal cancer cells. To investigate the impact of ciprofol on glycolysis and epithelial-mesenchymal transition (EMT) in colorectal cancer cells and its role in the Wnt/β-catenin signaling pathway. In vitro experiments were conducted utilizing cell counting kit-8 (CCK-8), scratch assays, and Transwell assays to assess the impact of ciprofol on the proliferation, invasion, and migration of colorectal cancer cells. Downregulation of adenomatous polyposis coli (APC) expression was utilized to ascertain the potential reversal of ciprofol's inhibitory effects. Lactate and glucose levels were assessed using assay kits in KYSE30 cells. Western blot analysis was employed to assess the expression levels of Wnt/β-catenin signaling pathway components, invasion-related proteins, and mRNA in colorectal cancer cells. In vivo experiments involved establishing a xenograft mouse model to verify the effects of ciprofol on HT29 cells. In vitro experiments demonstrated that ciprofol suppressed the EMT process and glycolysis in colorectal cancer cells. Ciprofol activated APC protein, and downregulation of APC mitigated the inhibitory effects of ciprofol on colorectal cancer cells. Ciprofol suppressed the Wnt/β-catenin signaling pathway, downregulated the protein expression of Hexokinase 2 (HK2), Lactate Dehydrogenase A (LDHA), Matrix Metalloproteinase 2 (MMP2), Matrix Metalloproteinase 9 (MMP9), and E-cadherin, and upregulated N-cadherin protein expression. In vitro experiments also revealed that ciprofol inhibited tumor growth in xenograft mice, with protein expression changes consistent with in vivo results. Ciprofol suppresses the EMT process and glycolysis in colorectal cancer cells. Furthermore, ciprofol may exert its anticancer effects by activating APC to inhibit the Wnt/β-catenin signaling pathway.