ETS-1:A Potential Target Of Glycolysis For Metabolic Therapy By Regulating Glucose Metabolism In Pancreatic Cancer

OBJECTIVEIn this study,we sought to identify the potential role for silencing ETS-1 in reducing the expression of glucose transporter 1(GLUT-1)to disturb glycolysis through alteration of "Warburg effect",by which could result in AMPK activation,autophagy induction and reduction of cell viability.METHODSMTT assay was applied to assess the cell viability in ETS-1 silencing cells and control groups.Glucose absorption rate,lactate production rate and cellular ATP level were measured by standard colorimetric assay kits.The levels of mRNAs of ETS-1,GLUT-1,ATG5 and ATG7 were analyzed by qRT-PCR.The expression of ETS-1,GLUT-1,ATG5,ATG7,p-AMPK,LC3II proteins were evaluated by western blot.RESULTS1.We found that cell viability was obviously attenuated after silencing ETS-1;2.Our results also showed that the expression of GLUT-1 significantly declined in ETS-1 silencing cell lines which resulted in a lower glucose utilization and lactate production.Furthermore,the inhibition of glycolysis,which depends on glucose utilization and lactate production,reduced the generation of energy in the form of ATP;3.The reduction of cellular ATP was associated with stimulation of AMP-activated protein kinase(AMPK)and induction of autophagy.CONCLUSIONOur results indicated that ETS-1 induced autophagy after inhibition of glycolysis,and thus led to comparatively decrease of cell viability.These results implied that ETS-1 could be a potential target for tumor metabolic therapy.