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Upregulation of CD54 and downregulation of HLA‑ABC contribute to the novel enhancement of the susceptibility of HL-60 cells to NK cell-mediated cytolysis induced by ATRA plus VPA.
- Source :
-
Oncology reports [Oncol Rep] 2017 Jan; Vol. 37 (1), pp. 105-114. Date of Electronic Publication: 2016 Nov 02. - Publication Year :
- 2017
-
Abstract
- Enhancement of the susceptibility of HL-60 cells to NK cell-mediated cytolysis induced by all-trans-retinoic acid (ATRA) plus valproate (VPA) was evaluated. In addition to the synergistic effect of ATRA plus VPA on HL-60 cells, the optimal concentration of 1 mM VPA plus 0.5 µM ATRA increased the cytotoxic sensitivity of HL-60 cells to NK cells. The expression of the activated receptors NKp30 and NKG2D on NK-92 cells was higher compared with the levels noted for the other receptors, and the expression of NKG2D ligands MICA/B on HL-60 cells was not significantly upregulated in the ATRA plus VPA goup compared with the control. Moreover, it was observed that the ligands of NKp30 on HL-60 cells presented the same variation trend. As to the co-stimulatory and adhesion molecules on NK-92 and their ligands on HL-60 cells post exposure to ATRA and VPA alone or their combination, there was no obvious change in the expression of CD112, CD48 and CD70 on the HL-60 cells. However, the expression of CD54 on HL-60 cells was significantly upregulated. In contrast, the expression of NKG2A ligands HLA-ABC on HL-60 cells was obviously downregulated. In addition, the expression of HLA-E on the HL-60 cells in the group treated with ATRA plus VPA was not significantly increased. In conclusion, the combination of VPA and ATRA not only induced the differentiation of HL-60 cells, but also induced enhancement of the sensitivity of HL-60 cells to NK cells by downregulating the expression of HLA-ABC and upregulating the expression of CD54, but not MICA/MICB. The results provide experimental and theoretical basis for the clinical combination of a low-dose of ATRA plus VPA for the treatment of leukemia.
- Subjects :
- Cells, Cultured
Down-Regulation drug effects
Drug Resistance, Neoplasm drug effects
Drug Resistance, Neoplasm genetics
Drug Resistance, Neoplasm immunology
Gene Expression Regulation, Leukemic drug effects
HL-60 Cells
HLA-A Antigens genetics
HLA-B Antigens genetics
HLA-C Antigens genetics
Humans
Intercellular Adhesion Molecule-1 metabolism
Killer Cells, Natural drug effects
Up-Regulation
Cytotoxicity, Immunologic drug effects
Cytotoxicity, Immunologic genetics
Intercellular Adhesion Molecule-1 genetics
Killer Cells, Natural immunology
Tretinoin pharmacology
Valproic Acid pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2431
- Volume :
- 37
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 27840957
- Full Text :
- https://doi.org/10.3892/or.2016.5212