Abstract:
To investigate the effects of sodium hydrogen exchange protein1 (Na+/H+ exchanger 1; NHE1)-specific inhibitor Cariporide on the in vitro metastasis of HeLa cells and to preliminarily explore the potential anti-metastasis mechanism of Cariporide. Methods: HeLa cells were treated with Cariporide, and its effects on the adhesion, migration, and invasion of HeLa cells were determined using cell-matrix adhesion assay, wound healing assay, and cell invasion assay. Real-time RT-PCR and Western blot assay were used to detect the effects of Cariporide on the levels of MT1-MMP ( membrane-type 1 matrix metalloproteinase ) mRNA and on the protein expression in the Hela cells, respectively. Results: The cell-matrix adhesion assay showed that the adhesive ratio of the HeLa cells treated with Cariporide was reduced by 25% compared with the controls. There were also significant differences between the two groups ( P < 0.05 ). The wound healing and cell invasion assays showed that after the Cariporide treatment, the healing speed of HeLa cell injury and the amount of the cells passing through the filter membrane were less in the treatment groups than in the control groups. RT-PCR and Western blot results showed that Cariporide produced a distinguished inhibition of MT1-MMP expression in HeLa cells, both on the mRNA and on the protein levels ( P < 0.05 ). Conclusion: Cariporide can inhibit the in vitro metastasis of HeLa cells effectively. The mechanism may be related to the downregulation of the expression of MT1-MMP.