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

Zou,Huijuan; Li,Lianlian; Han,Yang; Ma,Ruiping; Liao,Qiong; Tian,Jing; Zhang,Xiaoyu; Ren,Xia; Song,Guanhua; Guo,Qiang; Li,Xia; Ding,Huifang; Jiang,Guosheng

doi:10.3892/or.2016.5212

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

Authors:
- Huijuan Zou
- Lianlian Li
- Yang Han
- Ruiping Ma
- Qiong Liao
- Jing Tian
- Xiaoyu Zhang
- Xia Ren
- Guanhua Song
- Qiang Guo
- Xia Li
- Huifang Ding
- Guosheng Jiang
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Affiliations: Department of Hemato-Oncology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Key Medical Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology of Shandong, Jinan, Shandong 250062, P.R. China, School of Medicine and Life Sciences, University of Jinan‑Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China, Department of Oncology, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, P.R. China, Department of Hematology, Shengli Oilfield Central Hospital, Dongying, Shandong 257034, P.R. China
Published online on: November 2, 2016 https://doi.org/10.3892/or.2016.5212
Pages: 105-114

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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.

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