HPV16E7-HSP90 DNA疫苗治疗宫颈癌及其免疫机制的研究  

HPV16E7-HSP90 DNA Vaccine in Treatment of Cervical Cancer in Mice and Its Immunological Mechanism

作　　者：黄卓敏[1] 李晴 金平[1] 姚秀华[1] 

机构地区：[1]南方医科大学深圳市妇幼保健院

出　　处：《中国肿瘤》2018年第1期68-73,共6页China Cancer

基　　金：深圳市科技创新委员会2015立项课题(JCYJ20150402090413004)

摘　　要：[目的]探讨HPV16E7-HSP90 DNA疫苗用于治疗宫颈癌的疗效及其可能的免疫机制。[方法]建立TC-1宫颈癌细胞小鼠模型,负瘤第5d开始,随机将小鼠分为HPV16E7-HSP90 DNA疫苗组与对照组：DNA疫苗组给予DNA溶液100μl（5μg）,对照组给予磷酸盐缓冲溶液（PBS）100μl,两组均肌肉注射,每3d 1次,共4次。自负瘤第5d开始至治疗完成第8d,每3d测量肿瘤体积,绘制肿瘤生长曲线。治疗结束第8d,免疫组化方法检测小鼠肿瘤组织中CD8＋T细胞、肿瘤细胞凋亡分子FAS的表达情况,TUNEL法检测负瘤小鼠肿瘤细胞的凋亡率。[结果]HPV16E7-HSP90 DNA疫苗组的肿瘤生长速度明显低于PBS对照组（P〈0.05）。HPV16E7-HSP90 DNA疫苗组与对照组的小鼠宫颈癌组织中CD8＋T细胞表达的光密度平均值（MOD）分别为（8.76±1.27）vs（5.70±1.40）（P〈0.05）;肿瘤细胞FAS表达的MOD值分别为（8.73±0.99）vs（5.74±1.47）（P〈0.05）;小鼠肿瘤组织中CD8＋T细胞与FAS的表达呈正相关（P〈0.01）;HPV16E7-HSP90 DNA疫苗组与对照组小鼠肿瘤细胞的凋亡率分别为57.59%vs 13.11%（P〈0.05）。[结论 ]HPV16E7-HSP90 DNA疫苗可上调肿瘤细胞FAS的表达,促进肿瘤细胞凋亡,激活机体的CD8＋T细胞的免疫反应,从而产生明显的抗肿瘤效应,有望于未来用于宫颈癌及癌前病变的免疫治疗。[Purpose] To investigate the effectiveness of HPV16E7-HSP90 DNA vaccine in the treatment of cervical cancer in mice and its immunological mechanism.[Methods] On d5 after challenge of mouse cervical cancer TC-1 cells,mice were divided into two groups： HPV16E7-HSP90 DNA vaccine was intramuscularly injected to tumor-bearing mice in DNA vaccine group（5μg/mice,q3d ×4）,while PBS was injected to mice in control group（100μl/mice,q3d ×4）.The tumor volume was measured every 3d after tumor challenge and the tumor growth curve was drawn.The expression of CD8＋ T cells in tumor tissue and FAS protein in tumor cells were detected by immunohistochemical method at d8 after the completion of treatment.At the same time,the rate of apoptotic tumor cells was detected by TUNEL method.[Results] The tumor growth rate of the mice in DNA vaccine group was consistently lower than that in the control group（P〈0.05）.The expression of CD8＋T cells in the tumor tissues and the expression of FAS in the tumor cells in the DNA vaccine group were significantly higher than those in the control group[（8.76±1.27） vs（5.70±1.40）;（8.73±0.99） vs（5.74±1.47）;P〈0.05].The expressions of CD8＋T cells in tumor tissues was positively correlated with the expression of FAS in tumor cells（P〈0.01）.Meanwhile,the rate of apoptotic tumor cells in DNA vaccine group was significantly higher than that in the control group（57.59% vs 13.11%,P〈0.05）.[Conclusion] HPV16E7-HSP90 DNA vaccine shows a significant anti-tumor effect in tumor-bearing mice,which is associated with up-regulating of the expression of FAS,inducing the apoptosis of the tumor cells and improving the tumor specific immune responses of CD8＋T cells.

关 键 词：HPV16E7-HSP90 DNA疫苗 宫颈癌 免疫治疗 CD8+T细胞 FAS 凋亡 

分 类 号：R737.33[医药卫生—肿瘤]