Objective: To explore the molecular mechanisms of arsenic trioxide (As2O3) inhibiting NB4 cells proliferation.
Methods: The Janus kinase 1 (JAK1) protein level and its phosphorylation level in NB4 cells was detected by Western blots. NB4 cells were transfected with JAK1 siRNA or JAK1 plasmid to make JAK1 gene silenced or overexpressed. The inhibition of NB4 cells proliferation was measured by MTT assay and Trypan blue exclusion respectively. The variation of phosphorylation level of JAK1 and the cell cycle inhibitor P21 were determined by Western blots.
Results: JAK1 protein was expressed stably in NB4 cells, with no phosphorylation. The phosphorylation of JAK1 was enhanced after the NB4 cells treated with As2O3. After NB4 cells transfected with JAK1 siRNA, the expression level of JAK1 was obviously lower than that of in the non-specific siRNA group and blank control group. The effect of As2O3 inhibiting NB4 cells proliferation was weaker in the JAK1 siRNA transfected group. The inhibiting rate of 4 micromol/L As2O3 on NB4 cells proliferation of JAK1 siRNA group was 49.12% being lower than that of the non-specific siRNA group (74.58%) and control group (72.33%). After NB4 cells transfected with JAK1 plasmid, the JAK1 expression level in wild-type and mutant type plasmid groups were significantly higher than those in the empty plasmid group, moreover the effect of As2O3 inhibiting proliferation was stronger in wild-type plasmid group. The inhibiting rate of 4 micromol/L As2O3 on NB4 cells proliferation of wild-type plasmid group was 69.53% being higher than that of the mutant type JAK1 plasmid group (37.26%) and the empty plasmid group (39.61%). The expression level of P21 was up-regulated after the NB4 cells treated with As2O3.
Conclusion: JAK1 is expressed stably in NB4 cells, but has no activity. Arsenic trioxide inhibits the proliferation of NB4 cells through activating the JAK1. P21 is up-regulated after arsenic trioxide activated the JAK1 to inhibit the proliferation of NB4 cells.
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