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CN 22-1108/R
Volume 38 Issue 8
Aug.  2022
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Article Navigation >  Journal of Clinical Hepatology  > 2022  >  38(8): 1819-1824

Effect of naringenin on natural killer cell cytotoxicity against hepatocellular carcinoma cells in vitro and its mechanism

DOI: 10.3969/j.issn.1001-5256.2022.08.019
  • 1.

    Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

  • 2a.

    Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

  • 2b.

    Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

  • 3.

    Shanghai University of Medicine & Health Sciences, Shanghai 201203, China

Research funding:

General Project of National Natural Science Foundation of China (81874436);

The State "AIDS and Viral Hepatitis and Other Major Infectious Diseases Prevention and treatment" Science and Technology Major Project (2018ZX10725504);

Youth Project of National Natural Science Foundation of China (81904117)

More Information
  • Corresponding author: GAO Yueqiu, gaoyueqiu@hotmail.com(ORCID: 0000-0001-7276-9810)
  • Received Date: 2021-11-09
  • Accepted Date: 2022-02-28
  • Published Date: 2022-08-20
    Abstract
  •   Objective  To investigate the effect of naringenin on the killing rate of natural killer (NK) cells and related mechanism by amplification of human peripheral blood mononuclear cells into NK cells in vitro and co-culture with hepatocellular carcinoma (HCC) CLC5 cells at a ratio of 1∶ 1.  Methods  A lymphocyte separation medium was used to isolate human peripheral blood mononuclear cells, which were induced with recombinant human interleukin-2 in vitro to culture NK cells. CCK-8 assay was used to measure the proliferation of HCC cells after human HCC cells were treated with naringenin (0, 3.125, 6.25, 12.5, 25, and 50 μmol/L) for 0, 24, and 48 hours, and after human NK cells were treated with different concentrations of naringenin for 24 hours, CCK-8 assay was used to measure the proliferation of NK cells. CellTiter-LumiTM was used to measure the killing rate of NK cells after the NK-HCC cell co-culture system at the ratio of 1∶ 1 was treated with naringenin for 24 hours. Quantitative real-time PCR was used to measure the gene expression of the activating receptor NKG2D in NK cells and NKG2D ligands in HCC cells. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups.  Results  After being induced and cultured by recombinant human interleukin-2, NK cells were amplified to 82.33%±0.70% of human peripheral blood mononuclear cells. After naringenin treatment for 24 hours, there was no significant difference in the proliferation rate of HCC CLC5 cells between all mass concentration groups (all P > 0.05), and in the 25 and 50 μmol/L mass concentration groups, naringenin significantly promoted the proliferation of NK cells (both P < 0.000 1). After the NK-HCC cell co-culture system at the ratio of 1∶ 1 was treated with naringenin for 24 hours, there was a significant increase in the killing rate of NK cells in the 25 and 50 μmol/L mass concentration groups (both P < 0.000 1). After the co-culture system was treated with naringenin for 24 hours, naringenin had no effect on the expression of NKG2D in NK cells in the 25 and 50 μmol/L mass concentration groups, and it also had no effect on the expression of MICB and ULBP2 in HCC cells (all P > 0.05); it significantly upregulated the expression of the NKG2D ligands such as ULBP1 and ULBP3 in HCC cells (all P < 0.001).  Conclusion  Naringenin may increase the killing activity of NK cells by upregulating the expression of NKG2D ligands in HCC cells.

     

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