Our previous studies suggested a potential interaction between the POK erythroid myeloid ontogenic factor ZBTB7A and glucose transporter 1(GLUT1)in nasopharyngeal carcinoma(NPC).This study was designed to confirm the ...Our previous studies suggested a potential interaction between the POK erythroid myeloid ontogenic factor ZBTB7A and glucose transporter 1(GLUT1)in nasopharyngeal carcinoma(NPC).This study was designed to confirm the interaction and further evaluate the precise mechanism by which ZBTB7A and GLUT1 regulate NPC development.The binding sites between ZBTB7A and the promoter of GLUT1 were predicted by bioinformatics.Gene expression was measured by quantitative real-time polymerase chain reaction(qPCR),western blotting,and immunohistochemistry.The activities of key glycolysis enzymes,including hexokinase(HK),pyruvate kinase(PK),lactate dehydrogenase(LDH),and lactate,were detected using specific enzyme-linked immunosorbent assay kits.The connection between ZBTB7A and GLUT1 was analyzed by dual-luciferase reporter assay and chromatin immunoprecipitation-qPCR.The vitality,proliferation,and tumorigenicity of the cells expressing different levels of ZBTB7A were tested by adding the glycolysis inhibitor 2-deoxy-D-glucose(2-DG),followed by MTT,colorimetric focus forming,and xenograft assays,respectively.Our results showed that high expression of GLUT1 was associated with late-stage NPC.After constructing stably transfected cells with lentiviruses,ZBTB7A was effectively knocked down in 5-8F cells(RNAi-5-8F)and overexpressed in 6-10B cells(ZBTB7A-6-10B).The up-or downregulation of GLUT1 secondary to ZBTB7A changes was also limited.The vitality and proliferation of the cells expressing low ZBTB7A were notably blocked by 2-DG.The cells expressing high ZBTB7A were not very sensitive to 2-DG.The growth of RNAi-5-8F xenografts was strongly suppressed by 2-DG.The activities of HK,PK,and LDH were suppressed by 2-DG in the cells expressing low ZBTB7A.RNAi-5-8F cells had the lowest 2-DG-induced lactate production.ZBTB7A directly suppressed the promoter region of GLUT1 to regulate GLUT1 expression.Thus,ZBTB7A controls the 2-DG-induced inhibition of glycolysis by affecting GLUT1.展开更多
Beneficial effects of dietary energy restriction (DER), including extension of life-span, reduction in cancer risk, anti-cancer effects and decrease in age related neurodegenerative diseases have been well established...Beneficial effects of dietary energy restriction (DER), including extension of life-span, reduction in cancer risk, anti-cancer effects and decrease in age related neurodegenerative diseases have been well established. Given that DER is difficult to implement in humans due to practical constraints, development of energy restriction mimetics (ERMs) is considered as a suitable alternative. Our recent studies have established the anti-tumor effects of the dietary administration of the glycolytic inhibitor 2-deoxy-D-glucose, a potential ERM, an alternative to DER;without any adverse effects on general physiology. Since functioning of the brain is critically dependent on glucose, we investigated the effects of chronic dietary 2-DG administration on the behavioural outcome in mice. Our findings based on a battery of neuro-behavioural tests clearly suggest that the chronic dietary administration of 2-DG that appreciably impairs the process of tumorigenesis has no adverse effect on the cognitive, affective and sensory-motor functions. Together with the maintenance of normal physiology reported by us earlier, these observations strengthen the potential of dietary 2-DG as a safe cancer preventive strategy.展开更多
The title complex [Ni(TTA)2(DMSO)] (TTA = thenoyl trifluo-roacetone, DMSO=dimethyl sufloxide) belongs to triclinic, space group P1, parameters of crystal cell: a = 9.447(l), b = 10.505(1), c=11. 912(1)(?) , α=97. 42(...The title complex [Ni(TTA)2(DMSO)] (TTA = thenoyl trifluo-roacetone, DMSO=dimethyl sufloxide) belongs to triclinic, space group P1, parameters of crystal cell: a = 9.447(l), b = 10.505(1), c=11. 912(1)(?) , α=97. 42(1), β= 84. 00(1), γ = 102. 08(1)°, V = 1143. 3(?)3, Z = 2, Mr = 581. 22 [Ni (C8H4O2F3S)2(CH3)2SO)], Dc=1. 688g. cm-3, F(000) = 588, final R = 0. 065 and Rw = 0. 072 for 2873 reflections with I≥3σ(I). In the title complex the nickel atom has a square pyramidal geometry with four short Ni-O bonds and one long Ni -O (DMSO) bond.展开更多
基金The study was supported by the Natural Science Foundation of Guangxi Province(2016GXNSFBA380144)Guangxi Science and Technology Base and Talent Project(GuiKe-AD20297069)National Natural Science Foundation of China(81960493).
文摘Our previous studies suggested a potential interaction between the POK erythroid myeloid ontogenic factor ZBTB7A and glucose transporter 1(GLUT1)in nasopharyngeal carcinoma(NPC).This study was designed to confirm the interaction and further evaluate the precise mechanism by which ZBTB7A and GLUT1 regulate NPC development.The binding sites between ZBTB7A and the promoter of GLUT1 were predicted by bioinformatics.Gene expression was measured by quantitative real-time polymerase chain reaction(qPCR),western blotting,and immunohistochemistry.The activities of key glycolysis enzymes,including hexokinase(HK),pyruvate kinase(PK),lactate dehydrogenase(LDH),and lactate,were detected using specific enzyme-linked immunosorbent assay kits.The connection between ZBTB7A and GLUT1 was analyzed by dual-luciferase reporter assay and chromatin immunoprecipitation-qPCR.The vitality,proliferation,and tumorigenicity of the cells expressing different levels of ZBTB7A were tested by adding the glycolysis inhibitor 2-deoxy-D-glucose(2-DG),followed by MTT,colorimetric focus forming,and xenograft assays,respectively.Our results showed that high expression of GLUT1 was associated with late-stage NPC.After constructing stably transfected cells with lentiviruses,ZBTB7A was effectively knocked down in 5-8F cells(RNAi-5-8F)and overexpressed in 6-10B cells(ZBTB7A-6-10B).The up-or downregulation of GLUT1 secondary to ZBTB7A changes was also limited.The vitality and proliferation of the cells expressing low ZBTB7A were notably blocked by 2-DG.The cells expressing high ZBTB7A were not very sensitive to 2-DG.The growth of RNAi-5-8F xenografts was strongly suppressed by 2-DG.The activities of HK,PK,and LDH were suppressed by 2-DG in the cells expressing low ZBTB7A.RNAi-5-8F cells had the lowest 2-DG-induced lactate production.ZBTB7A directly suppressed the promoter region of GLUT1 to regulate GLUT1 expression.Thus,ZBTB7A controls the 2-DG-induced inhibition of glycolysis by affecting GLUT1.
文摘Beneficial effects of dietary energy restriction (DER), including extension of life-span, reduction in cancer risk, anti-cancer effects and decrease in age related neurodegenerative diseases have been well established. Given that DER is difficult to implement in humans due to practical constraints, development of energy restriction mimetics (ERMs) is considered as a suitable alternative. Our recent studies have established the anti-tumor effects of the dietary administration of the glycolytic inhibitor 2-deoxy-D-glucose, a potential ERM, an alternative to DER;without any adverse effects on general physiology. Since functioning of the brain is critically dependent on glucose, we investigated the effects of chronic dietary 2-DG administration on the behavioural outcome in mice. Our findings based on a battery of neuro-behavioural tests clearly suggest that the chronic dietary administration of 2-DG that appreciably impairs the process of tumorigenesis has no adverse effect on the cognitive, affective and sensory-motor functions. Together with the maintenance of normal physiology reported by us earlier, these observations strengthen the potential of dietary 2-DG as a safe cancer preventive strategy.
文摘The title complex [Ni(TTA)2(DMSO)] (TTA = thenoyl trifluo-roacetone, DMSO=dimethyl sufloxide) belongs to triclinic, space group P1, parameters of crystal cell: a = 9.447(l), b = 10.505(1), c=11. 912(1)(?) , α=97. 42(1), β= 84. 00(1), γ = 102. 08(1)°, V = 1143. 3(?)3, Z = 2, Mr = 581. 22 [Ni (C8H4O2F3S)2(CH3)2SO)], Dc=1. 688g. cm-3, F(000) = 588, final R = 0. 065 and Rw = 0. 072 for 2873 reflections with I≥3σ(I). In the title complex the nickel atom has a square pyramidal geometry with four short Ni-O bonds and one long Ni -O (DMSO) bond.
