The Inhibition Effects Of Selenomethionine Combined With 5-fluorouracil On Human Gastric Cancer MKN-45 Cells

Objective:To investigate the inhibition effects 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 inhibitory rates of proliferation of MKN-45 cells were detected by cell counting kit-8(CCK-8) method. The interaction of SeMet and 5-FU was estimated by Chou-Talalay method. The apoptosis rates, migration and invasion abilities of MKN-45 cells were detected by flow cytometry, migration assays and transwell assays, respectively. The expression levels of p53, p21, p27 and cyclin D1 proteins in MKN-45 cells were examined by Western blotting. Results:The proliferation inhibition 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 at different doses. The apoptosis rate of MKN-45 cells after treatment with combination of SeMet and 5-FU was higher than and cell migration and invasion abilities were lower than those of the control group and the single drug groups(P < 0.01). The expression levels of p53, p21, p27 proteins in combination group were significantly up-regulated as compared with those in the control group and the single drug groups(all P < 0.01), whereas the expressions of cyclin D1 protein was down-regulated(P < 0.01). Conclusion:SeMet in combination with 5-FU can synergistically inhibit the proliferation, migration, invasion and promote apoptosis of MKN-45 cells. This mechanism may be related to regulating the expressions of p53, p21, p27 and cyclin D1 proteins.