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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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    • References(22)
  • [1]
    Chinese Society of Hepatology, Chinese Medical Association. Consensus on the secondary prevention for primary liver cancer(2021 edition)[J]. J Clin Hepatol, 2021, 37(3): 532-542. DOI: 10.3969/j.issn.1001-5256.2021.03.008.

    中华医学会肝病学分会. 原发性肝癌二级预防共识(2021年版)[J]. 临床肝胆病杂志, 2021, 37(3): 532-542. DOI: 10.3969/j.issn.1001-5256.2021.03.008.
    [2]
    Professional Committee for Prevention and Control of Hepatobiliary and Pancreatic Diseases of Chinese Preventive Medicine Association; Professional Committee for Hepatology, Chinese Research Hospital Association; Chinese Society of Hepatology, Chinese Medical Association, et al. Guideline for stratified screening and surveillance of primary liver cancer(2020 edition)[J]. J Clin Hepatol, 2021, 37(2): 286-295. DOI: 10.3969/j.issn.1001-5256.2021.02.009.

    中华预防医学会肝胆胰疾病预防与控制专业委员会, 中国研究型医院学会肝病专业委员会, 中华医学会肝病学分会, 等. 原发性肝癌的分层筛查与监测指南(2020版)[J]. 临床肝胆病杂志, 2021, 37(2): 286-295. DOI: 10.3969/j.issn.1001-5256.2021.02.009.
    [3]
    National Health and Family Planning Commission of the P.R.C. Diagnosis, management, and treatment of hepatocellular carcinoma(V2017)[J]. J Clin Hepatol, 2017, 33 (8): 1419-1431. DOI: 10.3969/j.issn.1001-5256.2017.08.003.

    中华人民共和国国家卫生和计划生育委员会. 原发性肝癌诊疗规范(2017年版)[J]. 临床肝胆病杂志, 2017, 33(8): 1419-1431. DOI: 10.3969/j.issn.1001-5256.2017.08.003.
    [4]
    ZHONG XD, HE SQ, WEN B, et al. Mechanism of Biejiajian Wan against EMT of hepatocellular carcinoma cells through NF-κB signaling pathway[J]. Chin J Exp Med Formul, 2022, 28(1): 24-32. DOI: 10.13422/j.cnki.syfjx.20212421.

    钟晓丹, 贺松其, 文彬, 等. 鳖甲煎丸通过NF-κB信号通路抑制肝癌细胞上皮间质转化的作用机制[J]. 中国实验方剂学杂志, 2022, 28(1): 24-32. DOI: 10.13422/j.cnki.syfjx.20212421.
    [5]
    XIE CY, XIE G, JI YZ. Naringenin inhibits NLRP3 inflammasome through miR-22 and reduces intestinal barrier damage in a rat model of ulcerative colitis[J]. Chin J Pathophysiol, 2021, 37(9): 1573-1581. DOI: 10.3969/j.issn.1000-4718.2021.09.005.

    谢春燕, 谢刚, 季语竹. 柚皮素通过miR-22抑制NLRP3炎症小体并减轻溃疡性结肠炎大鼠模型肠屏障损伤[J]. 中国病理生理杂志, 2021, 37(9): 1573-1581. DOI: 10.3969/j.issn.1000-4718.2021.09.005.
    [6]
    JOSHI R, KULKARNI YA, WAIRKAR S. Pharmacokinetic, pharmacodynamic and formulations aspects of Naringenin: An update[J]. Life Sci, 2018, 215: 43-56. DOI: 10.1016/j.lfs.2018.10.066.
    [7]
    ZENG WF, ZHANG FY, DU GJ, et al. Research updates on a novel immunomodulator, naringenin[J]. Prog Biochem Biophysics, 2018, 45(9): 915-925. DOI: 10.16476/j.pibb.2018.0189.

    曾文峰, 张发云, 杜刚军, 等. 柚皮素: 新一代免疫调节剂[J]. 生物化学与生物物理进展, 2018, 45(9): 915-925. DOI: 10.16476/j.pibb.2018.0189.
    [8]
    BALD T, KRUMMEL MF, SMYTH MJ, et al. The NK cell-cancer cycle: advances and new challenges in NK cell-based immunotherapies[J]. Nat Immunol, 2020, 21(8): 835-847. DOI: 10.1038/s41590-020-0728-z.
    [9]
    XU L, WANG Y, CHEN FX, et al. The effect of wogonin on NK cell cytotoxicity against gastric cancer MKN45 cells in vitro and the mechanism[J]. Immunol J, 2014, 30(9): 804-808. DOI: 10.13431/j.cnki.immunol.j.20140176.

    许琳, 王营, 陈复兴, 等. 汉黄芩素对人NK细胞杀伤胃癌MKN45细胞的影响及其机制研究[J]. 免疫学杂志, 2014, 30(9): 804-808. DOI: 10.13431/j.cnki.immunol.j.20140176.
    [10]
    XU Z, ZHU X, SU L, et al. A high-throughput assay for screening natural products that boost NK cell-mediated killing of cancer cells[J]. Pharm Biol, 2020, 58(1): 357-366. DOI: 10.1080/13880209.2020.1748661.
    [11]
    MORVAN MG, LANIER LL. NK cells and cancer: you can teach innate cells new tricks[J]. Nat Rev Cancer, 2016, 16(1): 7-19. DOI: 10.1038/nrc.2015.5.
    [12]
    BALD T, KRUMMEL MF, SMYTH MJ, et al. The NK cell-cancer cycle: advances and new challenges in NK cell-based immunotherapies[J]. Nat Immunol, 2020, 21(8): 835-847. DOI: 10.1038/s41590-020-0728-z.
    [13]
    WANG S, LONG S, WU W. Application of traditional Chinese medicines as personalized therapy in human cancers[J]. Am J Chin Med, 2018, 46(5): 953-970. DOI: 10.1142/S0192415X18500507.
    [14]
    HUANG Y, ZHU J, LIN X, et al. Potential of fatty oils from traditional chinese medicine in cancer therapy: a review for phytochemical, pharmacological and clinical studies[J]. Am J Chin Med, 2019, 47(4): 727-750. DOI: 10.1142/S0192415X19500381.
    [15]
    CUI GT, SHAO M, SHI HL. Shao Ming's experience in treating primary liver cancer[J]. J Changchun Univ Chin Med, 2020, 36(3): 439-441. DOI: 10.13463/j.cnki.cczyy.2020.03.010.

    崔桂婷, 邵铭, 史会连. 邵铭论治原发性肝癌[J]. 长春中医药大学学报, 2020, 36(3): 439-441. DOI: 10.13463/j.cnki.cczyy.2020.03.010.
    [16]
    GHANBARI-MOVAHED M, JACKSON G, FARZAEI MH, et al. A systematic review of the preventive and therapeutic effects of naringin against human malignancies[J]. Front Pharmacol, 2021, 12: 639840. DOI: 10.3389/fphar.2021.639840.
    [17]
    ERDOGAN S, DOGANLAR O, DOGANLAR ZB, et al. Naringin sensitizes human prostate cancer cells to paclitaxel therapy[J]. Prostate Int, 2018, 6(4): 126-135. DOI: 10.1016/j.prnil.2017.11.001.
    [18]
    ALBAYRAK D, DOǦANLAR O, ERDOǦAN S, et al. Naringin combined with NF-κB inhibition and endoplasmic reticulum stress induces apoptotic cell death via oxidative stress and the PERK/eIF2α/ATF4/CHOP axis in ht29 colon cancer cells[J]. Biochem Genet, 2021, 59(1): 159-184. DOI: 10.1007/s10528-020-09996-5.
    [19]
    SHI GH, ZHOU SP, XU DS, et al. Killing effect of amplified NK cells on gastric cancer cells and its mechanism[J]. J Jilin Univ (Med Edit), 2020, 46(3): 530-535, insert 6. DOI: 10.13481/j.1671-587x.20200317.

    石光环, 周世平, 徐东升, 等. 扩增的NK细胞对胃癌细胞的杀伤作用及其机制[J]. 吉林大学学报(医学版), 2020, 46(3): 530-535, 后插6. DOI: 10.13481/j.1671-587x.20200317.
    [20]
    WU HF, ZHANG DY, ZHANG HY, et al. Effect and mechanism of IL-2 combined with IL-27 on natural killer cell against colorectal cancer cells[J]. Chin J Gerontol, 2021, 41(24): 5749-5752. DOI: 10.3969/j.issn.1005-9202.2021.24.069.

    吴红芳, 张冬云, 张海燕, 等. IL-2联合IL-27对NK细胞杀伤结直肠癌细胞的作用及机制[J]. 中国老年学杂志, 2021, 41(24): 5749-5752. DOI: 10.3969/j.issn.1005-9202.2021.24.069.
    [21]
    DING H, YANG X, WEI Y. Fusion proteins of NKG2D/NKG2DL in cancer immunotherapy[J]. Int J Mol Sci, 2018, 19(1): 177. DOI: 10.3390/ijms19010177.
    [22]
    LANIER LL. NKG2D receptor and its ligands in host defense[J]. Cancer Immunol Res, 2015, 3(6): 575-582. DOI: 10.1158/2326-6066.CIR-15-0098.
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