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10 November 2015 : Laboratory Research  

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

Yuping ZhangAB, Feizhou HuangCD, Jian WangBE, Hongwu LuoEF, Zhichao WangDFG

DOI: 10.12659/MSM.895034

Med Sci Monit 2015; 21:3442-3448


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.

MATERIAL AND 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.

Keywords: CASP8 and FADD-Like Apoptosis Regulating Protein - metabolism, Adenosine Triphosphate - chemistry, Deoxyglucose - chemistry, Gene Silencing, Liver Neoplasms - pathology, Membrane Potentials, Mitochondria - pathology, RNA, Small Interfering - metabolism, Receptor-Interacting Protein Serine-Threonine Kinases - metabolism, TNF-Related Apoptosis-Inducing Ligand - metabolism

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Med Sci Monit 2024; 30:e944927

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750