JNK信号通路对肝癌小鼠PGE2及CD4＋CD25＋调节性T细胞表达的影响

摘要

目的：探讨c-Jun氨基末端激酶（ JNK）信号通路对肝癌小鼠PGE2以及CD4＋CD25＋调节性T细胞表达的影响。方法 BALB／c小鼠肝癌移植瘤模型分为实验组与对照组，分别用SP600125多肽和生理盐水处理24 d， RT-PCR法检测各组JNK，ELISA法检测PGE2，流式细胞术和免疫组化法分别检测小鼠外周血和肝癌组织中CD4＋CD25＋调节性T细胞。结果实验组JNK表达低于对照组（0．68±0．03比0．98±0．17，P＜0．05）。实验组组织中PGE2的表达低于对照组[（4．64±0．36）ng／g比（6．64±1．24）ng／g，P＜0．05）]；实验组外周血PGE2的表达低于对照组[（76．57±10．16）pg／mL比（107．88±16．13）pg／mL），P＜0．05]；在肝癌组织中，实验组CD4＋CD25＋调节性T细胞所占百分比低于对照组[（14．37±3．35）％比（30．90±4．19）％，P＜0．05]；在外周血中，实验组CD4＋CD25＋调节性T细胞所占百分比低于对照组[（3．20±0．12）％比（4．22±0．32）％），P＜0．01]。结论阻断肝癌小鼠JNK信号通路可使PGE2表达下降，进而引起CD4＋CD25＋调节性T细胞水平降低。%Objective To investigate the influence of c-Jun N-terminal kinases ( JNK) signaling pathway on PGE2 and CD4 +CD25 +T regulatory T cells expression of mice with liver cancer.Methods The liver cancer xenograft models of BALB/c mice were divided into the experimental group and control group.Mice in each group were treated with SP600125 polypeptides or normal saline respectively for 24 days.RT-PCR was used to detect the expression of JNK pathway signal, ELISA was used to detect the PGE2 levels, and flow cytometry and immunohistochemistry were used respectively to detect CD4 +CD25 +T regulatory T cells levels in the peripheral blood and liver cancer tissues.Results The expression of JNK signaling pathway in the experimental group was lower than that of the control group [(0.68 ±0.03) vs.(0.98 ±0.169), P<0.05].The level of PGE2 was lower in the experimental group as compared with that of the control group [(4.64 ± 0.36) ng/g vs.(6.64 ±1.24) ng/g, P<0.05].In the periphery blood, PGE2 level of the experimental group was lower than that of the control group [(76.57 ±10.16) pg/ml vs.(107.88 ±16.13) pg/ml, P<0.05].In the liver cancer tis-sues, the percentage of CD4 +CD25 +T regulatory T cells of the experimental group was decreased as compared with that of the control group [(14.37 ±3.35)% vs.(30.90 ±4.19)%, P<0.01].In the peripheral blood, the percentage of CD4 +CD25 +T regulatory T cells of the experimental group was lower than that of the control group [(3.20 ±0.12)%vs. (4.22 ±0.32)%, P<0.05].Conclusion When JNK signaling pathway was blocked, the expression level was down-regulated, and consequently the levels of CD4 +CD25 +T regulatory T cells decreased.