Weichang'an suppressed migration and invasion of HCT116 cells by inhibiting Wnt/β-catenin pathway while upregulating ARHGAP25
| Autor: | Jin-Kun Yang, Li Tao, Ying Gu, Yingjie Zhu, Jian Zheng |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Small interfering RNA
Cell Biomedical Engineering Bioengineering MMP9 Applied Microbiology and Biotechnology Structure-Activity Relationship Downregulation and upregulation Cell Movement Drug Discovery medicine Humans Wnt Signaling Pathway beta Catenin Cell Proliferation Dose-Response Relationship Drug Activator (genetics) Chemistry Process Chemistry and Technology GTPase-Activating Proteins Wnt signaling pathway General Medicine Transfection HCT116 Cells Up-Regulation medicine.anatomical_structure Catenin Cancer research Molecular Medicine Heterocyclic Compounds 3-Ring Biotechnology Drugs Chinese Herbal |
| Zdroj: | Biotechnology and applied biochemistryReferences. 66(5) |
| ISSN: | 1470-8744 |
| Popis: | Evidence suggests that Weichang'an (WCA) inhibited the metastasis of colorectal cancer (CRC) in vitro 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 in vitro. 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 (0.4 mg/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 in vitro. |
| Databáze: | OpenAIRE |
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