[Mechanisms of sorafenib induced NB4 cell apoptosis].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2015 Feb;23(1):77-82

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 ┬Ámol/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.

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Source
http://dx.doi.org/10.7534/j.issn.1009-2137.2015.01.015DOI Listing
February 2015
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