ObjectiveThis paper intends to explore the mechanism by which pachymic acid (PA) inhibits the proliferation and migration of colorectal cancer (CRC) cells through the glycogen synthase kinase 3β (GSK3β)/β-catenin signaling pathway.MethodsHuman colon cancer cell line HCT116 was cultured routinely and divided into four groups: control (NC) group (untreated), PA group (treated with 8.50 μmol/L PA for 24 h), 5-fluorouracil (5-FU) group (treated with 0.70 μg/mL 5-FU for 24 h), and PA+5-FU group (treated with 4.25 μmol/L PA and 0.35 μg/mL 5-FU for 24 h). The CCK-8 assay and cell colony formation assay were used to assess the effect of PA on the proliferation of HCT116 cells, respectively. A Transwell experiment was conducted to evaluate the effect of PA on the invasion of HCT116 cells. A cell scratch healing experiment was performed to detect the effect of PA on the migration of HCT116 cells. Western blotting was used to detect the effect of PA on the expression of GSK3β/β-catenin pathway related proteins GSK3β, phosphorylated β-catenin (p-β-catenin), β-catenin, CyclinD1, and c-Myc in HCT116 cells.ResultsPA has a dose-dependent effect on inhibiting the proliferation of HCT116 cells. Compared with the NC group, the number of cell clones formed in the PA group is significantly reduced (P<0.01), and the migration and invasion abilities of HCT116 cells are significantly weakened (P<0.01). The protein expression levels of GSK3β and p-β-catenin in HCT116 cells are significantly increased (P<0.01), while the protein expression levels of β-catenin, CyclinD1, and c-Myc are significantly decreased (P<0.01).ConclusionPA can inhibit the proliferation and migration of HCT116 cells by activating the GSK3β/β-catenin signaling pathway.