Recombinant human granulocyte-colony-stimulating factor increases the sensitivity of acute myeloid leukemia cells to arsenic trioxide and its possible mechanism
10.3781/j.issn.1000-7431.2019.11.045
- Author:
Andi WANG
1
Author Information
1. Department of Hematology, South Campus of Renji Hospital, Shanghai Jiao Tong University School of Medicine
- Publication Type:Journal Article
- Keywords:
Acute;
Aquaporin 9;
Arsenic trioxide;
Granulocyte colony-stimulating factor;
Leukemia;
Myeloid
- From:
Tumor
2019;39(4):280-291
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) combined with arsenic trioxide (ATO) (molecular formula: As2O3) on the proliferation and apoptosis of acute myeloid leukemia (AML) cells, and to explore the possible mechanisms. Methods: AML cells HL-60 and THP-1 were pre-treated with rhG-CSF (100 ng/mL), and then treated with different concentrations of As2O3. The relative proliferation rate was detected by CCK-8 method, while the apoptosis and cell cycle distribution were measured by FCM method. The expression levels of aquaporin 9 (AQP9) mRNA and protein in HL-60, THP-1 and acute promyelocytic leukemia NB4 cells as well as HL-60 and THP-1 cells treated with rhG-CSF (100 ng/ mL) were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. Results: RhG-CSF promoted the proliferation of HL-60 and THP-1 cells (both P < 0.01). Compared with the As2O3 group, rhG-CSF pre-treatment combined with 2 μmol/L As2O3 inhibited the proliferation of HL-60 and THP-1 cells (both P < 0.05), rhG-CSF combined with different concentrations of As2O3 increased the apoptotic rates of HL-60 and THP-1 cells (both P < 0.05). As2O3 caused G0/G1 arrest in HL-60 and THP-1 cells (both P < 0.05). rhG-CSF caused S-phase arrest in HL-60 and THP-1 cells (both P < 0.01), the effect was more obvious in rhG-CSF combined with As2O3 group (both P < 0.05). The expressions of AQP9 mRNA and protein in HL-60 and THP-1 cells were lower than those in NB4 cells (all P < 0.01). Compared with the untreated control group, 100 ng/mL rhG-CSF up-regulated the expression levels of AQP9 mRNA and protein in HL-60 and THP-1 cells (all P < 0.05). Conclusion: RhG-CSF can increase the sensitivity of non-M3 AML cells to As2O3, which may be associated with the up-regulation of AQP9 expression.
