Effects of forkhead box M1 regulates glucose transporter 1 expression on glucose metabolism and biological characteristics in gastric cancer cells

Abstract

Objective To investigate the effect of forkhead box M1 (FOXM1) on the glucose metabolism, proliferation and apoptosis through regulating the expression of glucose transporter 1 (GLUT1) in gastric cancer cells. Methods The expression levels of FoxM1 and GLUT1 were detected by Western blotting and real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) in three cells (AGS, SGC-7901 and GES-1). To detect the change of expression of FoxM1, GLUT1 and glucose uptake, the FoxM1 over-expression vector and small interfering RNA (siRNA) were transfected into gastric cancer cells. Cell proliferation was detected by cell counting kit-8 (CCK-8) assay, apoptosis was detected by flow cytometry. Results The expression of FoxM1 mRNA in AGS and SGC-7901 cells were 2.624±0.167, 3.023±0.159 (t=16.686, P=0.004; t=21.810, P=0.002), and the expression of GLUT1 mRNA were 3.582±0.237 and 3.867±0.285 (t=18.700, P=0.003; t=17.315, P=0.003), which were significantly higher than those in GES-1. FoxM1 protein in AGS and SGC-7901 were higher than in GES-1 (2.852±0.271, 2.533±0.243 vs. 1±0.017, t=11.814, P=0.007; t=10.900, P=0.008). GLUT1 protein in AGS and SGC-7901 were higher than in GES-1 (3.716±0.316, 3.367±0.335 vs. 1.000±0.021, t=14.854, P=0.005; t=12.214, P=0.007). The results showed that GLUT1 expression, glucose uptake (t=3.242, P=0.048; t=3.964, P=0.029), AGS proliferation after transfected for 48 h and 72 h (t=10.062, P=0.002; t=6.466, P=0.008) were significantly increased and apoptosis was decreased [(1.36±0.29)% vs. (3.16±0.32)%, t=-7.219, P=0.006] by over-expression of FoxM1. Knockdown of FoxM1 decreased GLUT1 expression, glucose uptake (t=-4.217, P=0.024; t=-3.879, P=0.030), AGS proliferation after transfected for 48 h and 72 h (t=-10.280, P=0.002; t=-12.530, P=0.001) and increased apoptosis [(8.02±0.69)% vs. (3.03±0.26)%, t=11.722, P=0.007]. Conclusion FoxM1 can increase glucose uptake, cell proliferation and inhibit apoptosis through regulating the expression of GLUT1 in gastric cancer cells. Key words: Gastric cancer; Forkhead box M1; Glucose transporter 1; Glucose metabolism