肿瘤疫苗联合节拍化疗对小鼠乳腺癌作用的研究  

Anti-tumor effect of tumor vaccine combined with metronomic chemotherapy on breast cancer in mice

作　　者：史业辉[1] 周立艳[1] 魏枫[1] 于津浦[1] 贾勇圣[1] 佟仲生[1] 

机构地区：[1]天津医科大学肿瘤医院乳腺肿瘤内科、国家肿瘤临床医学研究中心、乳腺癌防治教育部重点实验室、天津市肿瘤防治重点实验室、津市肿瘤免疫与生物治疗重点实验室,津市300060

出　　处：《中国肿瘤临床》2014年第8期489-492,共4页Chinese Journal of Clinical Oncology

基　　金：天津市科技计划项目(编号:12ZCDZSY16200);天津市卫生局科技基金(编号:2010KZ76);天津市高等学校科技发展基金计划项目(编号:20100116)资助~~

摘　　要：目的:研究新型肿瘤疫苗联合节拍化疗对晚期乳腺癌小鼠模型的治疗效果,并探讨其作用机制。方法:以小鼠乳腺癌细胞系4T1接种Balb/c小鼠建立模型。利用含高迁移率核小体蛋白1(high-mobility group nucleosome binding protein 1,HMGN1)基因的重组质粒转染4T1细胞,制备瘤苗。小鼠皮下接种4T1细胞,随机分成生理盐水对照组(NS组)、吉西他滨节拍化疗组(MET组)、瘤苗组、节拍化疗联合瘤苗组(联合组)4组。观察各组小鼠肿瘤生长及不良反应,并检测肿瘤局部调节性T细胞(regu-latory T cells,Tregs)的Foxp3表达及肿瘤微血管密度(microvessel density,MVD)的变化。结果:联合组肿瘤体积明显小于MET组及瘤苗组(P<0.05),与NS组比较有显著性差异(P<0.001)。Western blot和免疫组织化学检测发现,联合组与MET组小鼠肿瘤局部浸润Tregs的Foxp3表达及肿瘤MVD明显减少(P<0.05)。各治疗组未出现明显的不良反应。结论:HMGN1基因修饰的新型瘤苗联合吉西他滨节拍化疗在乳腺癌小鼠模型治疗中疗效显著且耐受性良好。Objective：This study aimed to observe the synergistic effect of a new tumor vaccine combined with metronomic che-motherapy in vivo on breast cancer. This study was also conducted to investigate the mechanism of this combination. Methods：Balb/c mice inoculated with 4T1 mouse breast cancer cell were used as tumor models. High-mobility group nucleosome-binding protein 1 （HMGN1） gene was used to transfect 4T1 cell lines as cancer vaccines. After 4T1 cell was inoculated, the mice were randomized into four groups：normal saline （NS）;metronomic gemcitabine （GEM） alone;cancer vaccine alone;and combination therapy group. Tumor growth and potential toxicities of these regimens were observed. The Foxp3 expression of regulatory T cells （Tregs） was detected by western blot and immunohistochemical staining. The microvessel density （MVD） of the tumor was also detected by immunohistochemi-cal staining. Results：The tumor volume of the mice was significantly lower in the combination group than in the MET group or cancer vaccine group （P〈0.05）. This result exhibited a higher significant difference than the tumor volume of the mice in the NS group （P〈0.01）. Foxp3 expression was significantly lower in the mice treated with GEM （combination or MET group）. MVD was significantly lower in these two groups than in the cancer vaccine group or NS group （P〈0.05）. Furthermore, adverse reactions slightly occurred in each group. Conclusion： The combination of cancer vaccines and metronomic GEM is a very active and well-tolerated regimen for breast cancer in mice.

关 键 词：肿瘤疫苗HMGNl 节拍化疗 调节性T细胞 FOXP3 

分 类 号：R737.9[医药卫生—肿瘤]