摘要
目的研究抗CTLA-4(cytotoxic T lymphocyte antigen-4,CTLA-4)抗体(9H10)对小鼠Lewis肺癌的抑瘤作用及其机制。方法选取健康适龄C57小鼠,皮下接种小鼠Lewis肺癌细胞系,建立皮下移植瘤模型。12只荷瘤小鼠分为2组,分别为空白对照组和实验组,分别腹腔注射给予生理盐水和CTLA-4抗体(9H10),通过肿瘤体积、重量及肿瘤生长抑制率评估9H10的抑瘤作用;免疫组织化学染色检测脾组织T细胞亚型(CD4及CD8阳性T细胞)及肿瘤微血管密度(MVD),通过组间对照分析抗CTLA-4对肿瘤微环境免疫细胞及血管生成的影响。结果 CTLA-4抗体可延缓荷瘤小鼠的肿瘤生长速度,延长其生存时间。免疫组织化学染色检测荷瘤小鼠脾脏中CD4及CD8阳性T细胞。结果显示,实验组与对照组CD4阳性T细胞的数量分别为(49.05±7.31)%和(23.45±8.06)%,与对照组比较,应用抗CTLA-4处理后CD4表达阳性率明显增高,具有统计学意义(P<0.01)。实验组和对照组中CD8表达的阳性率分别为17.25±2.86和11.32±0.71,与对照组比较,应用抗CTLA-4处理后CD8表达的阳性率明显增高,具有统计学意义(P<0.05)。用抗CD34单克隆抗体标记肿瘤微血管内皮细胞,计数肿瘤间质MVD。实验组和对照组的MVD值分别为37.20±2.84和75.72±14.49,CTLA-4使肿瘤MVD明显减少,具有统计学意义(P<0.001)。结论CTLA-4抗体对荷瘤小鼠Lewis肺癌具有抑制作用,荷瘤小鼠脾组织中CD4及CD8表达均增高,肿瘤间质的MVD值显著降低。CTLA-4在提供机体抗肿瘤免疫及抑制肿瘤血管生成中均发挥重要作用。
Objective To investigate the antitumor effects of cytotoxic T lymphocyte antigen-4 antiboby（9H10）on mice Lewis lung cancer.Methods The transplantation tumor models were established by injection of Lewis lung cancer cells subcutaneously to C57BL/6 mice.Twelve mice were randomly divided into two groups：The 9H10 therapy group with intraperitoneal injection of cytotoxic T lymphocyte antigen-4 antibody and the control group with the injection of 0.9% sodium chloride respectively.The antitumor effects were investigated by measuring tumor volume,the dynamic change of tumor weight and the inhibition rate of tumor growth.The expression ratio of CD4 and CD8 positive T cells in spleen were detected by immunohistochemistry.Microvessel density （MVD）was assessed by CD31 immunostaining. Results The growth rate of tumor bearing mice were delayed and the survival time were prolonged.The CD4 positive T cells in the spleen of tumor bearing mice were 49.05±7.31% and 23.45±8.06% in 9H10 group and control group respectively.The positive rate of CD4 T cells were significantly increased comparing with control group after CTLA-4 antibody treatment （P 〈0.01）.The CD8 positive T cells were 17.25±2.86 and 11.32±0.71 in 9H10 group and con-trol group respectively.The positive rate of CD8 T cells were significantly increased in the experimental group than in the control group（P 〈0.05）.The tumor interstitial microvessel density （MVD）were 37.20±2.84 和 75.72±14.49 in the experimental group and control group respectively.The MVD significantly decreased after CTLA-4 antibody treat-ment （P 〈0.01）.Conclusion The growth of Lewis lung cancer were inhibited after CTLA-4 antibody treatment.The expression ratio of CD4 and CD8 positive T cells were both increased and the MVD value was lowered in the spleen of Lewis cancer bearing mice after CTLA-4 antibody treatment.CTLA-4 may play significant roles both on increasing the tumor immune and inhibiting tumor angiogenesis.
出处
《中国实验诊断学》
2015年第4期532-536,共5页
Chinese Journal of Laboratory Diagnosis
基金
吉林省科技厅自然科学基金资助课题(20130102084JC)
吉林大学白求恩医学科研支持计划资助课题(2013101005)
吉林大学"大学生创新创业训练计划"国家级项目资助课题(2013A71249)
