IL-27 promotes anti-tumor effect of NK92 cells by up-regulating expression of activated receptors and STATs phosphorylation
10.3872/j.issn.1007-385x.2019.05.003
- VernacularTitle:IL-27通过促进活化性受体表达和STATs磷酸化增强NK92细胞的抗肿瘤 作用
- Author:
SUN Yufei
1
;
JIANG Yanan
1
;
YU Huaihai
1
;
WANG Yufang
2
,
3
;
FU Qiang
4
Author Information
1. Department of Immunology, Binzhou Medical University,
2. Department of Clinical Laboratory, Fushan People&rsquo
3. s Hospital
4. Department of Immunology, Binzhou Medical University, 3. University of North Carolina Lineberger Cancer Center, Chapel Hill 27514, USA
- Publication Type:Journal Article
- Keywords:
IL-27;
NK92;
JAK-STATs;
anti-tumor
- From:
Chinese Journal of Cancer Biotherapy
2019;26(5):500-505
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the molecular and signal pathway mechanism of Interleukin-27 affecting the anti-tumor effect of NK92 cells. Methods: NK92 cells were cultured with different concentrations of IL-27 (10, 20, 30 and 60 ng/ml) for 24 hours. The cytotoxicity of NK92 cells to target cells was detected by LDH assay. The expressions of NKG2D, NKp30 and NKp46 on the surface of NK92 cells and the secretion of perforin and granzyme B were detected by Flow cytometry. The expression and phosphorylation level of STATs protein was detected by WB. The DU145 cell transplanted tumor model of prostatic carcinoma in NOD-PrkdcscidIl2rgem1/Smoc mice was established and treated with the combination of NK92 cells and IL-27 to evaluate their anti-tumor efficacy. Results: IL-27 at concentrations of 10, 20 and 30 ng/ml could significantly increase the cytotoxicity of NK92 cells to target cells, and 30 ng/ml exerted the best effect (P<0.05 or P<0.01). 30 ng/ml IL-27 could significantly promote the expressions of NKG2D, NKp30 and NKp46 on surface of NK92 cells, as well as elevate the secretion of perforin (all P<0.05), but didn’t affect the secretion of granzyme B (P>0.05); moreover, it also up-regulated the phosphorylation of STAT1, STAT3 and STAT5 protein (all P<0.01). The combined treatment of IL-27 and NK92 cells obviously extended the survival time of tumor-bearing mice (P<0.05). Conclusions: IL-27 can promote the cytotoxicity of NK92 cells against solid tumor cells and blood tumor cells by promoting expressions of NKG2D, NKp30 and NKp46 on the surface of NK92 cells and the secretion of perforin, which might be related with the phosphorylation of STAT1, STAT3 and STAT5 in JAKSTAT pathway.
- Full text:20190503.pdf
