Abstract
Evidence suggests that Weichang'an (WCA) inhibited the metastasis of colorectal cancer (CRC) invitro and downregulates oncogenic β-catenin; more intriguingly, we also found an upregulation of ARHGAP25 in this process. This study aimed to investigate the mechanisms by which WCA regulated CRC metastasis invitro. Here, HCT116 cells were transfected with siRNAs to interfere ARHGAP25 expression. WCA decoction, XAV939 (a specific Wnt/β-catenin pathway inhibitor), and LiCl (an activator for Wnt/β-catenin pathway) were used for treatment. Cell migratory and invasive capacities were determined using Transwell chamber. The activation of Wnt/β-catenin pathway was assessed by determining the expression of MMP7, MMP9, ZEB1, and β-catenin. The study suggests that WCA inhibited the migration and invasion of HCT116 cells and suppressed the activation of Wnt/β-catenin pathway, as evidenced by retarding MMP7, MMP9, ZEB1, and β-catenin. However, siRNA-ARHGAP25 resulted in the opposite. In siRNA-ARHGAP25-transfected HCT116 cells, WCA (0.4mg/mL) induced the antimetastatic effects and the inactivation of Wnt/β-catenin pathway was remarkably reversed with additional LiCl treatment. Our study concludes that inhibiting Wnt/β-catenin pathway while promoting ARHGAP25 was the mechanism, whereby WCA retarded migration and invasion of CRC invitro.
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