三氧化二砷降低结肠癌肺转移小鼠调节性T细胞的实验研究

发布时间：2018-01-01 18:00

  本文关键词：三氧化二砷降低结肠癌肺转移小鼠调节性T细胞的实验研究　出处：《大连医科大学》2015年硕士论文　论文类型：学位论文

  更多相关文章： 三氧化二砷结肠癌肺转移调节性 T 细胞

【摘要】：目的:探讨三氧化二砷(arsenic trioxide,As2O3)对小鼠结肠癌肺转移灶局部浸润调节性T细胞(regulatory T cells,Tregs)的影响以及对肿瘤免疫微环境的调节作用。方法:1)经尾静脉注射CT26细胞构建小鼠结肠癌高Tregs肺转移模型;2)实验分组:对照组生理盐水200ul/D/只,低剂量As2O3连续治疗组3mg/kg/D/只,高剂量As2O3间歇治疗组6mg/kg/D/只,治疗2周;3)不同浓度As2O3作用于细胞因子诱导的杀伤性细胞(Cytokine-induced killer,CIKs),实验分组,对照组生理盐水组、低浓度As2O3组0.1umol/l、中浓度As2O3组1.0umol/l、高浓度As2O3组5.0umol/l。结果:1)小鼠结肠癌肺转移模型建模成功,3天肺部即可出现转移灶,成瘤率100%;15天后,流式鉴定肺脏、脾脏Tregs与对照组相比差异显著(p0.05);外周血Tregs无显著性。2)体内实验结果:(1)As2O3治疗组能明显提高肺转移小鼠体重(p0.01),两治疗组之间差异显著(p0.01);As2O3治疗组显著降低肺转移结节数目及肿瘤负荷(p0.01),两治疗组之间差异不显著(p0.05)。(2)As2O3治疗组能显著降低转移肺组织中Tregs比例(p0.01),并且两治疗组之间差异显著(p0.05)。(3)As2O3治疗组能引起淋巴细胞在肺转移小鼠体内的重新分布,表现为T淋巴细胞在转移肺中升高(p0.01)、外周血中升高(p0.01)、脾中降低(p0.01),但两组之间差异不显著(p0.05);3)As2O3能显著降低CIKs中Tregs比例(p0.01),各处理组之间差异显著(p0.05);并且能增强CIKs细胞体外杀伤活性,表现为中、高浓度组CIKs细胞毒活性显著提高(p0.01),并且各浓度组之间差异显著(p0.01)。结论:As2O3体外可降低CIKs中Tregs比例,提高CIKs的杀伤活性;体内可通过降低Tregs比例、调节淋巴细胞在体内的重新分布来发挥抗肿瘤效应。
[Abstract]:Objective: to study arsenic trioxide (as _ 2O _ 3) arsenic trioxide. As _ 2O _ 3 (as _ 2O _ 3) could induce regulatory T cell regulatory T cells in lung metastases of colon cancer in mice. Methods mice colon cancer model with high Tregs lung metastasis was established by injecting CT26 cells via caudal vein and regulating tumor immune microenvironment. 2) the experimental group: the control group was 200 mL / D, and the low dose As2O3 group was 3 mg / kg / D / mouse. High dose As2O3 intermittent treatment group 6 mg / kg / d for 2 weeks; 3) different concentrations of As2O3 acted on cytokine-induced killer cells (Cytokine-induced kill cells). Control group, saline group, low concentration of As2O3 group 0.1 umol / L, moderate concentration of As2O3 group 1.0 umol / l. Results the lung metastasis model of mice with colon cancer and lung metastasis was successfully established for 3 days, and the tumorigenesis rate was 100%. 15 days later, compared with the control group, the Tregs of the spleen was significantly different from that of the control group (p 0.05). The results of in vivo experiment showed that the weight of mice with lung metastasis could be significantly increased in the treatment group treated with as _ 2O _ 3 (P _ (0.01)). The difference between the two groups was significant (p0.01). The number of metastatic nodules and tumor load were significantly decreased in As2O3 group (P 0.01). There was no significant difference between the two treatment groups (p0.05). The ratio of Tregs in metastatic lung tissue was significantly decreased in the treatment group (p0.01). The difference between the two treatment groups was significant (P 0.05). The treatment group could induce the redistribution of lymphocytes in mice with lung metastasis. The results showed that T lymphocytes increased p0.01 in metastatic lung, increased p0.01 in peripheral blood and decreased p0.01 in spleen, but there was no significant difference between the two groups. 3As2O3 could significantly reduce the proportion of Tregs in CIKs (p0.01), and the difference among the treatments was significant (p0.05). In addition, the cytotoxicity of CIKs cells in vitro was enhanced in the medium and high concentration groups, and the cytotoxic activity of CIKs cells was significantly increased in high concentration group (P 0.01). Conclusion: in vitro, as _ 2O _ 3 can reduce the proportion of Tregs in CIKs and increase the killing activity of CIKs. The anti-tumor effect can be played by reducing the proportion of Tregs and regulating the redistribution of lymphocytes in vivo.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.35

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