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[Study on the potential mechanisms of leukemia cell resistance to TRAIL-induced apoptosis]
Ji-hui Hao1, Xi-shan Hao, Ming Yu
1Central Laboratory, Tianjin Cancer Hospital, Tianjin 300060, China.
Objective:
To explore the potential mechanisms of leukemia cell resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) -induced apoptosis.
Methods:
Cells apoptosis, changes of mitochondrial membrane potential, activity of NF-kappaB, activity of caspase-8 and expressions of apoptosis-related proteins in TRAIL treated K562 and CEM cells, were detected by flowcytometry, ELISA and Western blotting methods, respectively.
Results:
After treated with TRAIL, the apoptosis indexes were 29.98% and 14.1%, and mitochondrial membrane potential were decreased to 73.25% and 25.4% in K562 and CEM cells respectively. Constitutive level of caspase-8 expression in CEM was lower than that in K562 cells. Both cells became over-expressed Bcl-xL and down-regulated Bax. The ratio of Bcl-xL/Bax in CEM cells was higher than that in K562 cells. Compared with that in K562, the NF-kappaB activity increased significantly in CEM after treatment with TRAIL in early stage.
Conclusion:
CEM cells were more resistant to TRAIL-induced apoptosis than K562 cells did. The potential mechanisms associated with CEM drug resistance might be the lower expression of the constitutive level of caspase-8, lower sensitivity of mitochondrial inner membrane, early increase in NF-KB activity and altered expression of Bcl-2 proteins family.
Insights
CEM cells exhibit greater resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis than K562 cells. Mechanisms include lower caspase-8, altered mitochondrial potential, and increased NF-kappaB activity in CEM cells.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Context:
- Leukemia treatment often involves apoptosis-inducing agents.
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising therapeutic candidate.
- Understanding resistance mechanisms is crucial for improving TRAIL-based therapies.
Purpose:
- To investigate the molecular mechanisms underlying leukemia cell resistance to TRAIL-induced apoptosis.
- To compare the sensitivity of K562 and CEM leukemia cell lines to TRAIL.
- To identify key proteins and pathways involved in TRAIL resistance.
Summary:
- CEM cells demonstrated significantly higher resistance to TRAIL-induced apoptosis compared to K562 cells.
- Key resistance factors in CEM cells included lower constitutive caspase-8 expression, reduced mitochondrial membrane potential sensitivity, early NF-kappaB activation, and an altered Bcl-xL/Bax ratio.
- These findings highlight specific molecular targets for overcoming TRAIL resistance in leukemia.
Impact:
- Provides insights into differential TRAIL sensitivity in leukemia subtypes.
- Identifies potential therapeutic targets to enhance TRAIL efficacy.
- Contributes to the development of more effective leukemia treatment strategies.
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