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2-DG-Regulated RIP and c-FLIP Effect on Liver Cancer Cell Apoptosis Induced by TRAIL
Yuping Zhang1, Feizhou Huang1, Jian Wang2
1Department of Normal Surgical, The 3rd Xiangya Hospital of Central South University, Changsha, Hunan, China (mainland).
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.
Insights
2-deoxy-D-glucose (2-DG) enhances TRAIL-induced liver cancer cell apoptosis by downregulating RIP and c-FLIP. This combination therapy reduces cell survival and mitochondrial potential, offering a potential anticancer strategy.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Cancer cell survival relies on glucose metabolism and ATP.
- Inhibiting glucose metabolism is a potential anticancer strategy.
- 2-deoxy-D-glucose (2-DG) disrupts normal glycometabolism and affects ATP levels, potentially regulating RIP and c-FLIP.
Purpose of the Study:
- Investigate the effect of 2-DG on RIP and c-FLIP expression in HepG2 and Hep3B liver cancer cells.
- Elucidate the mechanism of 2-DG in enhancing TRAIL-induced apoptosis.
- Assess the combined effect of 2-DG and TRAIL on liver cancer cell apoptosis.
Main Methods:
- Established RIP and c-FLIP gene-silenced HepG2 and Hep3B cell models using siRNA.
- Assessed cell viability via MTT assay and apoptosis rate by flow cytometry.
- Measured mitochondrial membrane potential using a JC-1 fluorescent probe.
Main Results:
- Both 2-DG and TRAIL alone reduced cell survival and promoted apoptosis.
- The combination of 2-DG and TRAIL significantly decreased cell survival and increased apoptosis compared to TRAIL alone.
- This combined treatment led to decreased mitochondrial membrane potential, dependent on Caspases, and inhibited RIP and c-FLIP expression.
Conclusions:
- 2-DG down-regulates RIP and c-FLIP expression in liver cancer cells.
- 2-DG modulates Caspase activity, enhancing TRAIL-induced apoptosis.
- The findings suggest 2-DG as a potential therapeutic agent to augment TRAIL-based liver cancer treatment.
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