Evodiamine inhibits migration and invasion of colorectal cancer SW480 cells via suppressing NF-κB-p65 signaling pathway

Abstract

Objective To investigate the effect of evodiamine (EVO) on the migration and invasion of colorectal cancer SW480 cells and explore the underlying mechanism. Methods SW480 cells were treated with different concentrations(0, 0.375, 0.75, 1.5, 3, 6, 12 μmol/L) of EVO for 24, 48, or 72 h, and the cell inhibition was detected using CCK-8 assay. SW480 cells treated with different concentrations of EVO for 24 h were examined for changes in migration and invasion using wound healing assay and Transwell assay and also for expression of IκBα, p-IκBα, NF-κB-p65, p-NF-κB-p65, MMP-9, MMP-2 and MMP-13 using Western blotting. Immunofluorescence staining was used to detect the expression of p-NF-κB-p65 and MMP-9 in SW480 cells treated with EVO for 24 h. The effects of lipopolysaccharide (LPS) challenge of SW480 cells prior to treatment with 1.5 μmol/L EVO on the expressions of IκBα, p-IκBα, NF-κB-p65, p-NF-κB-p65, MMP-9 and MMP-2 were investigated using Western blotting. Results EVO inhibited the proliferation of SW480 cells in a time-and dose-dependent manner. EVO treatment also dose-dependently inhibited the migration ability (P < 0.01) and invasion (P < 0.01) of SW480 cells, and significantly inhibited NF-κB-p65 signaling (P < 0.05). The inhibitory effect of EVO on NF-κB-p65 signaling was obviously attenuated by LPS challenge of the cells (P < 0.05). Conclusion EVO can inhibit the expression of MMP-9 via suppressing NF-κB-p65 signaling, and then cause ultimately inhibition of the migration and invasion of SW480 cells.

Keywords

• evodiamine
• nuclear factor-κb-p65
• matrix metalloproteinase-9
• colorectal cancer
• migration
• invasion