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Archive > Volume 20 Issue 6 > 2013,20(6):679-684. DOI:10.3872/j.issn.1007-385X.2013.06.008 Prev Next
Basic Research
Parthenolide inhibits proliferation of CD34+CD38- KG-1a leukemia cells and enhances susceptibility of CD34+CD38- KG-1a leukemia cells to the cytotoxicity of allo-NK cells
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Abstract:
Objective:To investigate the effects of parthenolide (PTL) on the proliferation, bcl-2 expression and susceptibility of CD34+CD38- KG-1a leukemia cells to cytotoxicity of allogeneic natural killer cells (allo-NK cells). Methods: CD34+CD38- KG-1a cells were separated from KG-1a cells by magnetic activated cell sorting (MACS). The effect of PTL on the proliferation of CD34+CD38- KG-1a cells was assessed by XTT assay. The expression of Bcl-2 mRNA and protein in CD34+CD38- KG-1a cells regulated by parthenolide were evaluated by real-time reverse transcriptase-polymerase chain reaction analysis (RT-PCR) and Western blotting, respectively. LDH-releasing assay was performed to observe the effect of PTL on the cytotoxicity of allo-NK cells against CD34+CD38- KG-1a cells. Results: PTL inhibited the proliferation of CD34+CD38- KG-1a cells with a concentration-dependent manner. As the concentration of PTL was 2.5 μmol/L, the cellular proliferation inhibition rate of CD34+CD38- KG-1a cells in PTL group was significantly higher than that of the control group (\[4.89±1.07\]% vs 0, P＜0.01). The IC50 of PTL to inhibit the proliferation of CD34+CD38- KG-1a leukemia cells was 20 μmol/L. By treated with 20 μmol/L PTL, the expression of bcl-2 mRNA (\[0.105±0007\] vs \[0.307±0.013\], P＜0.01) and protein in CD34+CD38- KG-1a cells were significantly lower than those of the control group. At effect-to-target ratio of 10∶1, 20∶1 and 40∶1, the cytotoxicity rate of allo-NK cell against CD34+CD38- KG-1a cells in the PTL group and in the positive control group was increasing and was higher than that of the negative control group (\[19.76±1.01\]%, \[30.14±0.96\]% and \[51.48±3.15\]% vs \[12.50±1.42\]%, \[16.90±093\]% and \[31.70±1.53\]%; all P<0.01). In addition, at effect-to-target ratio of 40∶1, the cytotoxicity rate of allo-NK cell against CD34+CD38- KG-1a cells in the PTL group was significantly higher than that of the positive control group (\[5148±315\]% vs \[43.08±2.81\]%, P<0.05). Conclusion: PTL can suppress the proliferation of CD34+CD38- KG-1a cells and enhance its susceptibility to the cytotoxicity of allo-NK cells, which may be related with the down-regulation of Bcl-2 by PTL．
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Project Supported:
Project supported by the Medical Research Foundation of Guangdong Province（No. A2012133）, and the Natural Science Foundation of Guangdong Province （No.S2012040007108）
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