Abstract: Objective To investigate the effect of propofol on the proliferation and invasion of colorectal cancer cells via regulating SFRP1-Wnt signaling pathway. Methods Colorectal cancer cell lines SW620 and HT29 were used, cells were divided into 2 groups: the control group and the propofol group. CCK-8 was used to detect cell proliferation activity. The wound-healing assay and transwell assay were used to analyze cell migration and invasion ability. Reverse transcription real-time fluorescence quantitative PCR was used to detect the expression levels of Wnt signaling pathway related genes. The chromatin immunoprecipitation assay was used to analyze the enrichment of EZH2 and H3K27Me3 in the SFRP1 promoter region. Results The proliferation activity of cells in the propofol group was significantly lower than that of the control group after propofol treatment for 24 hours (P< 0. 01). The wound-healing assay showed that the cell migration in the propofol group was significantly lower than that in the control group (P < 0. 01). The tranwell assay showed that the number of transmembrane cells in the propofol group was significantly less than that in the control group (P < 0. 01 ). qPCR resutls showed that E-cadherin was significantly up-regulated ( P < 0. 01), while N-cadherin was down-regulated (P < 0. 01) in the propofol group when compared with the control group. Wnt signaling pathway target genes β-catenin, c-Myc and Cyclin D1 was significantly down-regulated when compared with the control group (P < 0. 01). In addition, SFRP1, the upstream regulator of Wnt, was also significantly down-regulated in the propofol group ( P < 0. 01). Chromatin immunoprecipitation revealed that the enrichment of EZH2 and H3K27Me3 in the SFRP1 promoter was significantly lower in the propofol group than in the control group (P< 0. 01). Conclusion Propofol can inhibit the proliferation and invasion of colorectal cancer cells. Propofol attenuates the apparent silencing effect of EZH2 on SFRP1 and induces its upregulation, thereby reducing the activity of Wnt signaling pathway.

Key words: propofol, EZH2, SFRP1, Wnt signaling pathway, colorectal cancer, proliferation, metastasis, invasion