Abstract
The present study assessed the mechanism underlying the effect of sorafenib on the proliferation and apoptosis of the acute promyelocytic leukemia (APL) cell line NB4. NB4 cells were treated with different concentrations of sorafenib (0, 1.5, 3, 6, and 12 µM) for 24, 48 and 72 h. Cell proliferation, cell cycle, and apoptosis were analyzed using an MTT assay and flow cytometry analysis, respectively. Reverse transcription-semi-quantitative polymerase chain reaction and western blot analysis were performed to assess the expression of caspase-3, caspase-8, myeloid cell leukemia (MCL)1, cyclin D1, mitogen-activated protein kinase (MEK), phosphorylated (P)-MEK, extracellular signal-regulated kinase (ERK) and P-ERK. The results of the MTT assay demonstrated that, compared with untreated cells, the proliferation of sorafenib-treated NB4 cells was inhibited dose- and time-dependently. Furthermore, cell cycle arrest was induced in the G0/G1 phase and cell apoptosis was promoted in a dose-dependent manner in sorafenib-treated NB4 cells compared with untreated cells. In addition, the expression of the proapoptotic molecules caspase-3 and caspase-8 was significantly upregulated, and the expression of the antiapoptotic molecule MCL1 and the cell cycle-associated cyclin D1 was downregulated in sorafenib-treated NB4 cells compared with untreated cells. Furthermore, the phosphorylation of MEK and ERK was inhibited in sorafenib-treated NB4 cells compared with untreated cells. Sorafenib may inhibit proliferation and induce cell cycle arrest and apoptosis in APL cells. The underlying mechanisms of such effects may be associated with alterations to the expression of apoptosis-associated and cell cycle-associated molecules via MEK/ERK signaling pathway inhibition.