中国肿瘤生物治疗杂志2013，Vol.20Issue(1)：93-98,6.DOI:10.3872/j.issn.1007-385X.2013.01.016
IL-12诱导肝癌微环境中NK细胞活化发挥抗肿瘤作用
IL-12 plays anti-tumor effect by inducing NK cell activation in hepatic carcinoma microenvironment
摘要
Abstract
Objective: To explore the enhanced anti-tumor effect of IL-12 through inducing NK cell activition in hepatic carcinoma microenviroment. Methods: The hepatic cacinoma HepG2 cells were subcutaneously injected into NOD/SCID mice, and human peripheral blood lymphocytes (PBL) were introperitoneally injected after tumor formation to establish HCC-huPBL tumor-bearing mouse model. The tumor-bearing mice were randomized into IL-12 group and PBS control group. Mice were intratumoral injected with IL-12, and the changes of tumor volume and body weight as well as general conditions of tumor-bearing mice were observed. ELISA assay was performed to examine the expression levels of IL-12 and INF-7 in the microenvironment of hepatic carcinoma tissues in tumor-bearing mice, and the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in peripheral blood of mice 30 days after IL-12 intra-tumoral injection. Immunohistochemistry assay was used to analyze the expressions of NK-activating receptors; NKG2D, NKp44, NKp30, NKp46, and inhibitory NK receptors; KIR2DL3/CD158b and NKG2A/CD159a in hepatic carcinoma microenvironment after IL-12 treatment. Results; On day 12, 18, 24 and 30, the tumor volumes were smaller in the IL-12 group than those in the PBS group ([594. 47 ± 205. 51 ] vs [ 832. 10 ± 187. 49 ] mm3, [ 963. 61 ± 427. 95 ] vs [ 1 350. 87 ± 468. 23 ] mm3, [1 285. 02 ± 368. 56 ] vs [1 975. 49 ± 655. 54 ] mm3, [1 903. 64 ± 471. 34 ] vs [2 568.77 ±784.68] mm3, P＜0.05). The expression levels of IL-12 and IFN-7 in the IL-12 group were significantly higher than those in the PBS group ([2. 96 ±1.02] vs [1.35 ±0.75] pg/ml, [12.26 ±4. 11] vs [7.81 ±3.46] pg/ml, P ＜0. 05). The serum ALT level significantly increased in the IL-12 group compared to the PBS group on day 7 ([73. 85 ±10.71] vs [41.73 ±13.13] U/L, P＜0.05), and reached a peak at day 14. The expressions of NK-activating receptors NKG2D, NKp44 and NKp30 were statistically higher in the IL-12 group than those in the PBS group (P ＜ 0. 05 ) , the expression level of NKp46 showed no significant up-regulation, while the expression levels of NK inhibitory receptors CD158b and CD 159a were decreased compared to the PBS group ( P ＜ 0.05 ). Conclusion: IL-12 intratumoral injection can up-regulate the expressions of NK-activating receptors, IL-12 and IFN-γ, and down-regulate the NK inhibitory receptors in the hepatic carcinoma mouse model, therefore effectively inhibiting the tumor growth in mouse model.关键词
NK细胞/活化性受体/抑制性受体/IL-12/IFN-γ/移植性肝癌Key words
NK cell/ activatory receptor/ inhibitory receptor/ IL-12/ IFN-7/ transplanted hepatic carcinoma分类
医药卫生引用本文复制引用
周智锋,江金华,李洁羽,陈强,叶韵斌..IL-12诱导肝癌微环境中NK细胞活化发挥抗肿瘤作用[J].中国肿瘤生物治疗杂志,2013,20(1):93-98,6.基金项目
福建省卫生厅青年科研基金项目(No.2009-2-30) （No.2009-2-30）
福建省科技厅重点项目(No.200810012). （No.200810012）
