In this study,we investigated the effect and molecular mechanism of 8-O-acetylharpagide in colon cancer.Human colon cancer line HCT116 cell cycle was blocked in G1 phase after 8-O-acetylharpagide treatment.In addition,0.75 mmol/L 8-O-acetylharpagide significantly increased apoptosis of HCT116 cells.The whole transcriptome sequencing analysis showed that 8-O-acetylharpagide caused a total of 1 921 up-regulated mRNAs and 2 208 down-regulated mRNAs in HCT116 cells,and Wnt signaling pathway-related genes transcription level changed significantly.In cellular experiments in vitro,8-O-acetylharpagide treatment led to significant down-regulation of β-catenin,CyclinD1,Survivin,c-Myc and Bcl-2,while significant up-regulation of proapoptotic proteins Bax and cleaved-caspase3.Together,these results suggest that 8-O-acetylharpagide inhibit the proliferation and induce apoptosis of colon cancer cells mainly through Wnt signaling pathway.