The synergistic inhibition effect of selenomethionine combined with 5-fluorouracil on human gastric cancer MKN-45 cells

Objective: To investigate the inhibition effect of selenomethionine (SeMet) combined with 5-fluorouracil (5-FU) on human gastric cancer MKN-45 cells, and to explore the possible mechanism.Methods: The MKN-45 cells were treated with different concentrations of SeMet or 5-FU alone or in combination. The proliferation inhibitory rate of MKN-45 cells was detected by cell counting kit-8 (CCK-8) method. The interaction of SeMet and 5-FU was estimated by Chou-Talalay combination index method. The apoptosis and the migration and invasion abilities of MKN-45 cells were detected by flow cytometry, scratch-wound assay and Transwell chamber assay, respectively. The expression levels of p53, p21, p27 and cyclin D1 proteins in MKN-45 cells were examined by Western blotting.Results: The proliferation inhibitory rates of MKN-45 cells in single drug groups (SeMet or 5-FU) and the combination group (SeMet and 5-FU) were increased as compared with that in the control group (without any treatment) (P < 0.01) in a dose-dependent manner. SeMet and 5-FU had a synergistic effect. As compared with the control group and the single drug groups, the apoptosis rate of MKN-45 cells after treatment with combination of SeMet and 5-FU was increased and the migration and invasion abilities were decreased (all P < 0.01); the expression levels of p53, p21 and p27 proteins in combination group were significantly up-regulated (all P < 0.01), whereas the expression of cyclin D1 protein was down-regulated (both P < 0.01).Conclusion: SeMet in combination with 5-FU can synergistically inhibit the proliferation, migration and invasion of MKN-45 cells as well as promote apoptosis. This mechanism may be related to regulating the expressions of p53, p21, p27 and cyclin D1 proteins in MKN-45 cells. DOI:10.3781/j.issn.1000-7431.2015.11.091