Ann Med Med Res | Volume 5, Issue 1 | Research Article | Open Access
Jiu-Mei Shen1#, Rui Fan2#, Tao Wang3, Dong-Yan Shen2* and Zai-Fa Hong3*
1Department of Pathology, Xiamen Hospital of Traditional Chinese Medicine, China
2Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine,
Xiamen University, China
3Department of Hepato-Biliary-Pancreatic and Vascular Surgery, The First Affiliated Hospital of Xiamen University,
School of Medicine, Xiamen University, China
*Correspondance to: Dong-Yan Shen
Fulltext PDFBackground: Metastasis in Hepatocellular Carcinoma (HCC) is one of the main reasons for its
poor prognosis. Natural killer cells produce killing effects on tumor cells by secreting Interferon-γ
(IFN-γ), the mechanism of IFN-γ for hepatocellular carcinoma metastasis remain unclear. Here
we aimed to reveal the mechanism of interferon-γ secreted by natural killer cells in regulating
hepatocellular carcinoma metastasis.
Methods: Natural killer cells were isolated from blood samples of healthy volunteers. Wound healing
assay, transwell migration and invasion assays were applied to assess the ability of natural killer
cells and IFN-γ to inhibit hepatocellular carcinoma metastasis. Glucose uptake in hepatocellular
carcinoma cells measured with the Glucose Uptake Colorimetric Kit. Lactate levels and ATP
production in hepatocellular carcinoma cells measured with the L-lactate colorimetric kit and the
EnzyLightď›› ADP/ATP colorimetric kit, respectively. Interferon-γ mRNA levels were measured by
real-time quantitative Polymerase Chain Reaction (q-PCR), and interferon-γ protein levels were
analyzed by Enzyme-Linked Immunosorbent Serological Assay (ELISA). Western Blot (WB) was
used to detect the protein expression of Hexokinase 2 (HK2), Phosphoglycerate Kinase 1 (PCK1),
and Signal Transducer and Activator of Transcription 1 (STAT1). All experiments included
treatment and control groups, and at least three replicates. Results expressed as mean ± SD, and
statistical analysis performed using SPSS statistical software.
Results: We found that interferon-γ produced by natural killer cells inhibited the migration and
invasion of HCC by decreasing aerobic glycolysis. Furthermore, aerobic glycolysis of HCC in turn
inhibited interferon-γ secretion by natural killer cells through down-regulation of Signal Transducer
and Activator of Transcription 1 (STAT1) phosphorylation.
Conclusion: We reveal a unique mechanism that interferon-γ produced by natural killer cells
suppress the metastasis of hepatocellular carcinoma through inhibiting the glycolysis.
Natural killer cells; Hepatocellular carcinoma; Interferon-γ; Signal transducer and activator of transcription 1; Glycolysis
Shen J-M, Fan R, Wang T, Shen D-Y, Hong Z-F. IFN-γ Secreted by NK Cells Effectively Suppresses Metastasis of
Hepatocellular Carcinoma through Inhibiting Glycolysis. Ann Med Medical Res. 2022; 5: 1044..