| 低剂量环磷酰胺对小鼠脾脏Treg细胞影响及联合CIK细胞治疗小鼠肝癌的研究 |
| Alternative Title | Influence of low-dose cyclophosphamide on regulatory T cells in spleen of mice and it，s antitumor immunity combined with cytokine induced killer cells on hepatocellular carcinoma in mice
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| 周海静 |
| Subtype | 硕士
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| Thesis Advisor | 严祥
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| 2016-05-27
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| Degree Grantor | 兰州大学
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| Place of Conferral | 兰州
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| Degree Name | 硕士
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| Keyword | 环磷酰胺
肝细胞癌
调节性T细胞
细胞因子诱导的杀伤细胞
免疫治疗
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| Abstract | 目的 通过单次和循环应用环磷酰胺(cyclophosphamide, CTX)对荷瘤小鼠调节性T细胞(regulatory T cells, Tregs)的影响及联合细胞因子诱导的杀伤细胞(cytokine induced killer cells, CIKs)抗肿瘤的疗效，探讨CTX增强过继性细胞免疫治疗（adoptive cellular immunotherapy, ACI）抗肿瘤机制，为提高ACI抗肿瘤疗效提供思路。
方法 以C57BL/6小鼠为研究对象，将培养的Hepa1-6肝癌细胞注射于小鼠右侧腋下建立模型；观察CTX对脾脏Tregs的影响，计算肿瘤体积并绘制肿瘤生长曲线；体外培养CIKs；观察CTX联合CIKs治疗小鼠肝癌疗效时，将造模成功的荷瘤小鼠随机分为6组，分别用相应治疗方案干预后，隔天测量小鼠肿瘤长短径，计算肿瘤体积并绘制肿瘤生长曲线，实验结束时，剥离瘤块称重，计算抑瘤率。
结果 在CTX对脾脏Tregs影响实验中，循环CTX组Tregs维持在较低水平。在CTX联合CIKs治疗小鼠肝癌实验，循环CTX+CIKs组小鼠瘤体积及瘤重最小，循环CTX和单次CTX+CIKs组对肿瘤抑制效应较弱，单独CIKs和单次CTX组未能抑制肿瘤生长。
结论 随着肿瘤发展，小鼠脾脏中Tregs比例逐渐增加；循环应用CTX能够使Tregs维持在相对较低水平，因此在临床应用中更有价值；低剂量CTX通过调控Tregs，能显著提高CIKs的疗效，以循环应用CTX效果最好，为CTX调控Tregs的基础上联合ACI的临床应用提供理论依据。 |
| Other Abstract | Objective To explore the influence of single or cyclical CTX injection on regulatory T cells and it，s anti-tumor effect combined with cytokine induced killer cells(CIKs) on hepatocellular carcinoma(HCC) in mice.
Methods C57BL/6 mice were injected with Hepa1-6 cells to construct animal model, then we drawn the growth curve. In vitro we culture CIKs. In the end of the incubation, the proportion of CD8+NK1.1+ was detected and killing activity was detected by cell counting kit-8. In the therapeutic trial. We constrcted HCC model then randomly divide into 6 groups. We drawn the growth curve. At last, the tumor was weighed to calculated tumor inhibition rate.
Results Firstly, the Tregs in cyclical CTX group kept in low level; Lastly, The tumor volume and weight were minimum in the cyclical CTX + CIKs group. Cyclical CTX and single CTX+CIKs groups were weaker in tumor inhibition effect. But tumor in single CIKs and CTX groups were unsuppressed.
Conclusion Cyclical administration of low-dose CTX could kept Tregs at low level and enhanced the anti-tumor effect of CIKs by regulating Tregs, which provided a theoretical basis for the clinical application of CIKs combined with ACI. |
| URL | 查看原文
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| Language | 中文
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| Document Type | 学位论文
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| Identifier | https://ir.lzu.edu.cn/handle/262010/201244
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| Collection | 第一临床医学院
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Recommended Citation
GB/T 7714 |
周海静. 低剂量环磷酰胺对小鼠脾脏Treg细胞影响及联合CIK细胞治疗小鼠肝癌的研究[D]. 兰州. 兰州大学,2016.
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