Effect of arbutin on the malignant progression of gastric cancer cells by regulating the PI3K/Akt/GLUT1 signaling pathway
Objective To investigate the effect of arbutin(Arb)on malignant progression of gastric cancer cells by regulating the phosphatidylinositol 3 kinase/threonine protein kinase/glucose transporter 1(PI3K/Akt/GLUT1)signaling pathway.Methods SNU-601 cells were treated with different concentrations of Arg(12.5,25,50,100,200,400μmol/L),and cell activity was measured to screen the optimal concentration.SNU-601 cells were induced with blank control,low-dose,medium-dose and high-dose Arb,and high-dose Arb+PI3K/Akt activator 740 Y-P.Apoptotic rate,cell cycle,glucose uptake,lactate production,ATP production,cell migration and cell invasion were detected.Western blot was applied to detect the protein expressions of Bax,cleaved-caspase3,Bcl-2,p-PI3K,PI3K,p-Akt,Akt,GLUT1,and HK Ⅱ.Results Treatment of 12.5-400μmol/L Arg significantly inhibited the proliferation of SNU-601 cells.50,100,and 200 μmol/L of Arg were selected for the low-dose,medium-dose and high-dose in the subsequent experiments.Compared with those of blank control,SNU-601 cells induced with low-dose,medium-dose and high-dose Arb presented significantly lower cell viability,glucose uptake,lactate production,ATP production,migratory and invasive cell number,and protein levels of Bcl-2,p-PI3K/PI3K,p-Akt/Akt,GLUT1 and HK Ⅱ,but higher apoptotic rate and protein levels of Bax and cleaved-caspase 3(P＜0.05).Compared with high-dose Arb-induced cells,those induced with high-dose Arb+740 Y-P presented significantly higher cell viability,glucose uptake,lactate production,ATP production,migratory and invasive cell number,and protein levels of Bcl-2,p-PI3K/PI3K,p-Akt/Akt,GLUT1 and HK Ⅱ,but lower apoptotic rate and protein levels of Bax and cleaved-caspase 3(P＜0.05).Conclusion Arb inhibits the malignant progression of gastric cancer cells by inhibiting the PI3K/Akt/GLUT1 signaling pathway.
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