Abstract
Purpose: To observe the effects of paeonol on the invasion and migration of LoVo colorectal cancer cells, and investigate its possible mechanisms. Materials and Methods: Cell transwell assay and wound-healing assay were applied, and the results suggested that paeonol could significantly inhibit the invasion and migration abilities of LoVo cells, which was associated with a reduction in COX-2 expression and PGE2 synthesis. Treatment with the selective COX-2 inhibitor, celecoxib, or transient transfection of colorectal cancer cells with COX-2 siRNA, also inhibited cell invasion and migration. Results: The invasion and migration capacity were evaluated in LoVo cells by transwell assay and wound-healing in vitro. Compared with the control group, the invasion cells through Matrigel and the wound-healing rate were significantly decreased after treated with paeonol for 24 h. Paeonol treatment downregulated the expression of MMP-9 and downregulated the COX-2 expression and PGE2 synthesis in LoVo cells. Paeonol could up-regulate the expression of epithelial marker E-cadherin while down-regulate the expressions of mesenchymal markers, Fibronectin and Vimentin. Paeonol inhibited PI3K-Akt and MAPK-ERK pathways in LoVo cells. Celecoxib treatment significantly decreased the cells penetrating the matrigel in a dose-dependent manner. siRNA knockdown of COX-2 leaded to inhibition of cell invasion in LoVo cells. Knockdown of COX-2 increased the expression of E-cadherin, whereas the expressions of Fibronectin and Vimentin were downregulated. Conclusion: Paeonol may inhibit PI3K-Akt and MAPK-ERK pathways through suppressing of the COX-2 expression and PGE2 synthesis, thus inhibiting the cell invasion, migration, and EMT in LoVo cells.
Heterogeneous gene expression changes in colorectal cancer cells share the WNT pathway in response to growth suppression by APHS-mediated COX-2 inhibition