[Mechanisms of sorafenib induced NB4 cell apoptosis]
Yun-Jie Zhang1, Xin Liu2, Yan-Ping Song3
1Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University Medicial College, Xi'an 710061, Shaanxi Province, China; Xi'an Institute of Hematology, The Central Hospital of Xi'an, Xi'an 710003, Shaanxi Province, China.
Objective:
To investigate the effects of sorafenib on human acute promyelocytic leukemia cell NB4 and its mechanism.
Methods:
The human acute promyelocytic leukemia cell NB4 was treated with different concentrations (0, 1.5, 3, 6 and 12 µmol/L) of sorafenib, the proliferation inhibitory rate of NB4 cells was assayed by MTT, the apoptosis of NB4 was determined with flow-cytomatry after treatment; after extraction of total protein, the Western blot was performed to determine the expressions of apoptosis-relatived molecules Caspase-3, Caspase-8 and MCL-1. The mRNA expressions of Caspase-3, Caspase-8 and MCL-1 were determined by RT-PCR.
Results:
As compared with the control group, the proliferation of NB4 significantly decreased after treatment with different concentrations of sorafenib. The sorafenib significantly induced the apopotosis of NB4 cells in time- and dose-dependent manners. Furthermore, sorafenib treatment resulted in the obvious increase of the Caspase-3 and Caspase-8 protein and mRNA expressions, and down-regulated the MCL-1 protein and mRNA expressions in NB4 cells.
Conclusion:
Sorafenib can inhibit proliferation and induce apopotosis of human acute promyelocytic leukemia cell NB4 through the expression of Caspase-3 and Caspase-8, and down-regulation of the expression of MCL-1.
Insights
Sorafenib effectively inhibits acute promyelocytic leukemia cell growth and triggers apoptosis. This occurs via increased Caspase-3/Caspase-8 and decreased MCL-1 expression in NB4 cells.
Area of Science:
- Hematology
- Molecular Biology
- Cancer Research
Background:
- Acute promyelocytic leukemia (APL) is a subtype of leukemia.
- Targeted therapies are crucial for APL treatment.
- Understanding drug mechanisms is key to improving patient outcomes.
Purpose of the Study:
- To evaluate sorafenib's impact on human acute promyelocytic leukemia NB4 cells.
- To elucidate the molecular mechanisms underlying sorafenib's effects.
Main Methods:
- NB4 cells were treated with varying sorafenib concentrations.
- Cell proliferation was assessed using MTT assays.
- Apoptosis, Caspase-3, Caspase-8, and MCL-1 expression (protein and mRNA) were analyzed via flow cytometry, Western blot, and RT-PCR.
Main Results:
- Sorafenib significantly reduced NB4 cell proliferation in a dose-dependent manner.
- Sorafenib induced apoptosis in NB4 cells, with time- and dose-dependency.
- Sorafenib increased Caspase-3 and Caspase-8 expression while decreasing MCL-1 expression.
Conclusions:
- Sorafenib demonstrates potent anti-leukemic activity against NB4 cells.
- The drug inhibits proliferation and induces apoptosis by modulating Caspase-3, Caspase-8, and MCL-1.
- Sorafenib represents a potential therapeutic agent for acute promyelocytic leukemia.
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