2-DG-Regulated RIP and c-FLIP Effect on Liver Cancer Cell Apoptosis Induced by TRAIL

Source of support: Departmental sources Background: Cancer cells survival depends on glucose metabolism and ATP. Inhibiting glucose metabolism is a possible an-ticancer treatment. The phosphorylation of 2-deoxy-D-glucose (2-DG), which is a glycogen analogue, serious-ly 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. Material/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 fluores-cent 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, in-crease 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 cance