抗CTLA-4抗体联合阿霉素治疗小鼠乳腺癌的疗效及机制分析  

Effect and mechanism of combined therapy using anti-CTLA-4 antibody and doxorubicin on mice bearing breast cancer

作　　者：沈文状[1] 董鸿[1] 张林[1] 刘谨文[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院甲乳外科,武汉430030

出　　处：《重庆医学》2015年第23期3172-3175,共4页Chongqing medicine

基　　金：国家自然科学基金资助项目(81372204)

摘　　要：目的探讨抗细胞毒性T淋巴细胞相关抗原(CTLA-4)抗体联合阿霉素治疗小鼠乳腺癌的疗效及机制。方法以小鼠乳腺癌细胞系4T-1接种Balb/c小鼠建立模型,随机分为空白组、溶剂组、单用抗CTLA-4抗体组、单用阿霉素组、联合用药组。观察各组小鼠肿瘤生长,脾和骨髓的细胞亚型,对肿瘤微环境中凋亡细胞和微血管密度(MVD)进行检测。结果单用抗CTLA-4抗体组、单用阿霉素组、联合用药组小鼠肿瘤体积均显著低于空白组、溶剂组(P<0.05),且联合用药组小鼠肿瘤体积和质量显著低于单用抗CTLA-4抗体组、单用阿霉素组小鼠肿瘤体积(P<0.05)。与空白组、溶剂组相比,单用抗CTLA-4抗体组、单用阿霉素组和联合用药组的荷瘤小鼠脾中CD8+T和CD4+T细胞占淋巴细胞的百分比显著增高(P<0.05)。联合用药组肿瘤细胞凋亡的阳性百分率显著高于其他组(P<0.05)。联合用药组MVD显著低于其他组,且单用抗CTLA-4抗体组和单用阿霉素组MVD显著低于空白组和溶剂组(P<0.05)。结论联合抗CTLA-4抗体和阿霉素可在一定程度提高小鼠机体免疫力,明显抑制乳腺癌小鼠肿瘤生长,促进肿瘤微环境中肿瘤细胞凋亡,减少肿瘤微环境中微血管生成,效果优于单一用药。Objective To investigate the effect and mechanism of combined therapy using anti-CTLA-4antibody and doxorubicin on mice bearing breast cancer.Methods Balb/c mice inoculated with 4T-1mouse breast cancer cell were used as tumor models,which were randomly divided into blank group,solvent control group,anti-CTLA-4antibody only group,doxorubicin only group and combined therapy group.Tumor growth of mice was observed.The ratio of spleen and bone marrow cell subgroup were evaluated.Tumor microenvironment apoptosis and microvessel density（MVD）were evaluated.Results The tumor volume of anti-CTLA-4antibody only group,doxorubicin only group and combined therapy group were lower than those in the rest groups（P〈0.05）.The tumor volume and mass of combined therapy group was significantly higher than those of anti-CTLA-4antibody only group,doxorubicin only group（P〈0.05）.Compared with blank group,solvent control group,CD8＋Tand CD4＋T ratio in antiCTLA-4antibody only group,doxorubicin only group,combined therapy group increased with significant difference（P〈0.05）.The positive cell apoptosis rate of combined therapy group was significantly higher than those of other groups（P〈0.05）.The MVD of combined therapy group was significantly lower than those of other groups（P〈0.05）.The positive cell apoptosis rate and MVD of anti-CTLA-4antibody only group,doxorubicin only group were better than those of blank group,solvent control group.Conclusion Combined therapy using anti-CTLA-4antibody and doxorubicin could improve the immune,significantly inhibit the growth of tumor,promote cancer cell apoptosis and decrease MVD.

关 键 词：乳腺肿瘤 表柔比星 免疫 抗CTLA-4抗体 

分 类 号：R737.9[医药卫生—肿瘤]