title: 2-DG-Regulated RIP and c-FLIP Effect on Liver Cancer Cell Apoptosis Induced by TRAIL.
abstract: BACKGROUND
  Cancer cells survival depends on glucose metabolism and ATP. Inhibiting glucose metabolism is a possible anticancer treatment. The phosphorylation of 2-deoxy-D-glucose (2-DG), which is a glycogen analogue, seriously affects the normal glycometabolism phosphorylation process, leading to ATP consumption. Studies showed that 2-DG could regulate RIP and c-FLIP. This paper aimed to investigate the effect of 2-DG on RIP and c-FLIP expression in HepG2 and Hep3B cells, further illustrating the effect and mechanism of 2-DG regulating RIP and c-FLIP expression on liver cancer cell apoptosis induced by TRAIL.
  
  
  METHODS
  RIP and c-FLIP gene silencing HepG2 and Hep3B cell models were established by siRNA and detected by Western blot. Cell viability was determined by MTT and apoptosis rate was measured by flow cytometry. JC-1 fluorescent probe was used to test mitochondrial membrane potential.
  
  
  RESULTS
  2-DG or TRAIL alone significantly reduced HepG2 and Hep3B cell survival rate and promoted apoptosis. Compared with the single TRAIL treatment group, the combination of 2-DG and TRAIL could reduce cell survival rate, increase apoptosis rate, and decease mitochondrial membrane potential, which is dependent on Caspases. 2-DG can inhibit RIP and c-FLIP expression, leading to increased TRAIL-induced HepG2 and Hep3B cells apoptosis.
  
  
  CONCLUSIONS
  2-DG can down-regulate RIP and c-FLIP expression, and change Caspases activities to increase the liver cancer cell apoptosis induced by TRAIL.
authors.affiliation: Department of Normal Surgical, The 3rd Xiangya Hospital of Central South University, Changsha, Hunan, China (mainland).
authors.forename: Yuping
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Normal Surgical, The 3rd Xiangya Hospital of Central South University, Changsha, Hunan, China (mainland).
authors.forename: Feizhou
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Normal Surgical, Genetics Research Room of Central South University, Changsha, Hunan, China (mainland).
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Normal Surgical, The 3rd Xiangya Hospital of Central South University, Changsha, Hunan, China (mainland).
authors.forename: Hongwu
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Normal Surgical, The 3rd Xiangya Hospital of Central South University, Changsha, Hunan, China (mainland).
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism*; D003847:Deoxyglucose / Q000737:chemistry*; D005434:Flow Cytometry; D020868:Gene Silencing; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008564:Membrane Potentials; D008928:Mitochondria / Q000473:pathology; D034741:RNA, Small Interfering / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D053422:Receptor-Interacting Protein Serine-Threonine Kinases