Reduced Expression of Natural Killer Cell-Related Activating Receptors by Peripheral Blood Mononuclear Cells from Patients with Breast Cancer and Their Improvement by Zoledronic Acid

Document Type : Research Articles

Authors

1 Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman, Iran.

2 Department of Hematology-Oncology and BMT, Kerman University of Medical Sciences, Kerman, Iran.

3 Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

4 Department of Hematology and Laboratory Sciences, Para-Medical School, Kerman University of Medical Sciences, Kerman, Iran.

5 Department of Histology, School of Medicine, Islamic Azad University Branch of Kerman, Kerman, Iran.

6 Department of Immunology, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

Abstract

Background/aim: Natural killer (NK) cell receptors affect the NK cell-mediated elimination of malignant cells. In this experimental study the effect of Zoledronic acid (ZOL) was investigated on the expression of NK activating- (NKP46 and NKG2D) and inhibitory (KIR2DL1) receptors by Phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from breast cancer (BC) patients. Materials and Methods: Peripheral blood mononuclear cell-extracted RNA from thirty breast cancer women and twenty-five healthy subjects was analyzed for gene expression of NKP46, NKG2D and KIR2DL1 using real time-PCR. Then, the PBMCs from BC patients were cultured in the presence of PHA with 5 μg/ml, 10 or 20 μg/ml of ZOL for 32 hours and expression of the aforementioned receptors was determined. Results: Expression of NKP46, NKG2D and NKP46/KIR2DL1 ratio in BC women were lower than healthy group (P<0.01, P<0.04 and P<0.05, respectively). NKP46 expression was up-regulated by PHA-stimulated PBMCs treated with 10 μg/ml and 20 μg/ml of ZOL compared with PHA-stimulated cultures (P<0.01 and P<0.05, respectively). NKG2D expression remarkably increased by PHA-stimulated cultures treated with 5 μg/ml, 10 μg/ml and 20 μg/ml of ZOL compared with PHA-stimulated cultures (P<0.05 and P<0.02 and P<0.04, respectively). Conclusion: Expression of NK cell-related activating receptors decreased in BC patients. ZOL can improve the expression of NK activating receptors.

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