目的: 探讨清热解毒方对小鼠肝癌模型的抗肿瘤作用和淋巴细胞亚群、自然杀伤细胞家族2成员D(NKG2D)及其配体MULT1的影响。方法: 建立小鼠H22肝癌模型,观察清热解毒方的抗肿瘤效应。采用流式细胞术检测小鼠外周血淋巴细胞亚群和肿瘤组织、瘤旁NKG2D及其配体MULT1表达情况的变化。结果: 清热解毒方有一定抗肿瘤作用,且能改善荷瘤小鼠的体重降低;清热解毒方对小鼠外周血淋巴细胞亚群有一定影响,中药组较对照组B细胞、CD8+T细胞比例降低,CD3+T细胞比例、CD4+T/CD8+T增加(P<0.05);小鼠肝癌模型中,癌旁组织中NKG2D和MULT1阳性率均高于肿瘤组织,中药干预后,肿瘤组织和癌旁组织的NKG2D和MULT1阳性率均显著高于对照组(P<0.05)。结论: 清热解毒方抗肿瘤机制可能与增强NKG2D及其配体介导的抗肿瘤免疫反应,调节T淋巴细胞亚群平衡,改善免疫微环境有关,而NKG2D及其配体系统可作为肿瘤治疗及预后评估的潜在靶点。
Abstract
Objective: To investigate the anti-tumor effect of Qingre Jiedu formula (QRJD) on hepatocellular carcinoma in mice and the influence on NKG2D and its ligand MULT1. Methods: Mice models of H22 hepatocellular carcinoma were established. The anti-tumor effect of QRJD was observed. Distributions of peripheral blood lymphocyte subsets and expression of NKG2D/NKG2D-ligand were investigated by flow cytometry methods. Results: First, QRJD showed some anti-tumor effect, and could prevent weight loss of tumor bearing mice. Then, QRJD revealed influence on distributions of peripheral blood lymphocyte subsets, with the proportion of B cell, CD8+T cell decreased and CD3+T cell, CD4+T/CD8+T increased compared with the control group (P<0.05). Also, the expression of NKG2D/NKG2D-ligand in the tumor was lower than in adjacent tissues. The expression of NKG2D/NKG2D-ligand in the tumor and adjacent tissues of QRJD group was higher than that of control group (P<0.05). Conclusion: QRJD could enhance NKG2D/NKG2DL-mediated anti-tumor immune responses, regulate the balance of T lymphocyte subsets, and improve the immune microenvironment, which may be related to its mechanism on anti-tumor.
关键词
清热解毒方 /
原发性肝癌 /
自然杀伤细胞家族2成员D /
MULT1 /
免疫微环境
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Key words
Qingre Jiedu formula /
primary hepatocellular carcinoma /
NKG2D /
MULT1 /
immune microenvironment
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中图分类号:
R259
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脚注
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基金
*上海市自然科学基金(No.21ZR1463600),上海市卫生健康委员会临床研究专项(No.20224Y0059),上海中医药大学附属岳阳中西医结合医院院级课题重点项目(No.2017YJ01)
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