线粒体动力相关蛋白DRP1对肝癌细胞糖代谢的调控作用研究  

Regulation of mitochondrial dynamic-related protein 1 on glucose metabolism in liver cancer cells

作　　者：耿西林[1] 张颖[1] 李浩 张煜[1] 常虎林[1] GENG Xi-lin;ZHANG Ying;LI Hao;ZHANG Yu;CHANG Hu-lin(Department of Hepatobiliary Surgery,Shaanxi Provincial People's Hospital,Xi'an,Shaanxi 710032,China;不详)

机构地区：[1]陕西省人民医院肝胆外科,陕西西安710068 [2]西安医学院临床医学系,陕西西安710021

出　　处：《中华全科医学》2022年第1期35-38,共4页Chinese Journal of General Practice

基　　金：陕西省自然科学基金青年项目(2020JQ-948)。

摘　　要：目的探讨线粒体动力相关蛋白1(dynamic-related protein 1,DRP1)在肝癌细胞糖代谢重编程中的作用。方法(1)siRNA下调肝癌细胞SNU-739中DRP1表达后,检测对肝癌细胞葡萄糖摄取与乳酸产生的影响,以明确DRP1对肝癌细胞糖酵解的调控作用。(2)siRNA下调肝癌细胞SNU-739中DRP1表达后,检测对肝癌细胞氧耗速率与ATP产生的影响,以明确DRP1对肝癌细胞氧化磷酸化的调控作用。(3)siRNA下调肝癌细胞SNU-739中DRP1表达后,利用质谱检测对糖酵解与线粒体三羧酸循环代谢产物的影响。结果(1)下调DRP1可显著抑制肝癌SNU-739细胞的葡萄糖摄取(siCtrl:si-DRP1#1:si-DRP1#2=1.000±0.069:0.417±0.032:0.400±0.040;F=141.400,P<0.001)与乳酸产生(siCtrl:si-DRP1#1:si-DRP1#2=1.000±0.050:0.327±0.040:0.310±0.036;F=256.700,P<0.001)。(2)下调DRP1可激活肝癌SNU-739细胞的氧耗速率(siCtrl:si-DRP1#1:si-DRP1#2=1.000±0.069:1.623±0.081:1.591±0.046;F=81.720,P<0.001)与ATP产生(siCtrl:si-DRP1#1:si-DRP1#2=1.000±0.062:1.813±0.093:1.850±0.070;F=119.200,P<0.001)。(3)下调DRP1后,肝癌SNU-739细胞中糖酵解中间产物葡萄糖、丙酮酸与乳酸的水平均显著降低(均P<0.001),而三羧酸循环关键产物柠檬酸、延胡索酸与苹果酸的水平均显著升高(均P<0.001)。结论线粒体动力相关蛋白DRP1通过激活糖酵解并抑制氧化磷酸化而促进肝癌细胞的糖代谢重编程。Objective To explore the effect of mitochondrial dynamic-related protein 1(DRP1)on glucose metabolism reprogramming in liver cancer cells.Methods After DRP1 was knocked down by siRNA in liver cancer SNU-739 cells,(1)To explore the effect of DRP1 on glycolysis of liver cancer,glucose uptake and lactate production were determined.(2)To explore the effect of DRP1 on oxidative phosphorylation of liver cancer,the oxygen consumption rate and ATP production were determined.(3)The effects of DRP1 knockdown on the levels of metabolites in glycolysis and the TCA cycle were determined by mass spectrometry analysis.Results(1)Down regulation of DRP1significantly inhibited glucose uptake and lactate production in SNU-739 cells(siCtrl:si-DRP1#1:si-DRP1#2=1.000±0.069:0,417±0.032:0.400±0.040:F=141.400,P<0.001)and lactate production(siCtrl:si-DRP1#1:si-DRP1#2=1.00±0.050:0.327±0.040:0.310±0.036;F=256.700,P<0.001).(2)Down regulation of DRP1 markedly increased the rate of oxygen consumption(siCtrl:si-DRP1#1:si-DRP1#2=1.000±0.069:1.623±0.081:1.591±0.046;F=81.720,P<0.001)and ATP production(siCtrl:si-DRP1#1:si-DRP1#2=1.000±0.062:1.813±0.093:1.850±0.070;F=119.200,P<0.001).(3)Down regulation of DRP1 decreased the levels of glucose,pyruvate and lactate(all P<0.001)in glycolysis metabolism,but increased the levels of citrate,fumarate and malate(all P<0.001)metabolites in the TCA cycle.Conclusion DRP1 reprogrammed glucose metabolism of liver cancer cells through increasing glycolysis and decreasing oxidative phosphorylation.

关 键 词：线粒体动力相关蛋白 线粒体 糖酵解 氧化磷酸 肝癌 

分 类 号：R735.7[医药卫生—肿瘤] R730.231[医药卫生—临床医学]