Effects and Mechanism of PARP Inhibitor Olaparib on the Expression of NKG2D Ligands in HL-60 Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the regulatory effects of Olaparib on natural killer cell activating receptor (NKG2D) ligands expression on human acute myeloid leukemia (AML) cell line HL-60, and to explore the molecular mechanism of Olaparib on HL-60 cells.@*METHODS@#After HL-60 cells in logarithmic growth phase were treated with Olaparib at different concentrations for different times (24, 48 h), the expression of NKG2D ligand on the surface of HL-60 cells was detected by flow cytometry. Western blot was used to dectect the expression of ERK expression in HL-60 cells. The killing effect of NK cells to HL-60 cells was detected by CFSE/PI method.@*RESULTS@#10 μmol/L Olaparib could upregulate the expression of NKG2D ligand on the surface of HL-60 cell at 24 and 48 hours, while 5 μmol/L Olaparib could induce up-regulation of the expression of ULBP-2 and ULBP-3 at 48 hours. Western blot analysis showed that ERK phosphorylation of HL-60 cells was enhanced after treating with Olaparib. The killing effect of NK cells to HL-60 cells could be enhanced by Olaparib, however, ERK inhibitor could suppress the killing effect of NK cells to HL-60 cells.@*CONCLUSION@#Olaparib can upregulate NKG2D ligands expression on the surface of HL-60 cells and enhance the cytotoxicity of NK cell to HL-60 cells. The mechanism may be related to Olaparib promoting ERK phosphorylation expression.

Effects of matrine on the expression of NKG2D ligands in leukemia cells / 中国实验血液学杂志

This study was aimed to analyze the expression of NKG2D ligands in human leukemic cells and to investigate the effects of matrine on NKG2D ligand expression. The expressions of NKG2D ligand MICA/B, ULBP1-3 in several human leukemia cell lines (K562, OUN-1, U937 and K562/AO2), as well as primary leukemic cells isolated from malignant leukemia patients were analyzed by flow cytometry. After treatment with different doses of matrine, the expression level of NKG2D ligands in these leukemic cells was detected by FCM. The results indicated that NKG2D ligand expression was detected in both the leukemia cell lines and primary malignant leukemic cells. Generally, the expression of ULBP was high or obviously higher than that of MICA/B in leukemia cell lines and primary leukemic cells. The expression pattern of NKG2D ligands was different among these cells, possibly due to the different types of leukemia. Not all the expression of NKG2D ligands was upregulated after matrine treatment. Much higher expressions of ULBP2 and ULBP3 were found in K562 cells, compared to the other cell lines, which partly contributes to the higher sensitivity of K562 cells to NK cytotoxicity as target cells. It is concluded that there is universal expression of NKG2D ligand in leukemia cells. The high ULBP expression is prevalent in human leukemia cells. Matrine has the potential to induce the expression of NKG2D ligands in leukemia cells.