摘要
目的探讨高迁移率族蛋白B1(HMGB1)分子与人乳头瘤病毒(HPV)16型E6E7重组腺病毒载体疫苗免疫效果的关系及机制。方法通过TC-1细胞移植诱导建立小鼠肿瘤模型,在接种HPV重组腺病毒载体疫苗的同时,给予注射HMGB1特异性拮抗剂HMGB1 A box,开展肿瘤抑制试验、小鼠免疫状态观察、肿瘤相关信号检测等研究。结果 A box蛋白与疫苗联用,可显著降低模型小鼠HMGB1血清水平,抑制肿瘤组织中NF-?B的m RNA高表达,提高疫苗的抗肿瘤活性。同时,它还可减少IL-4、促进IFN-?产生,使体内免疫平衡由Th2向Th1偏移。和肿瘤模型对照组相比,在接种疫苗并注射A box蛋白后,由肿瘤引起的NF-?B、Bcl-2、c-IAP2、VEGF、MMP-9的表达提高、Bax表达降低均得到显著扭转。结论 HMGB1分子可以削弱HPV重组腺病毒载体疫苗的免疫效果,其机制可能是HMGB1在调节免疫平衡状态及控制肿瘤细胞的凋亡、浸润、转移等多层面均能参与并发挥重要作用。
OBJECTIVE To study the influence of HMGB1 on the effect of recombinant adenovirus vector-based human papillomavirus-16 vaccine in mice model and explore the potential mechanism. METHODS HMGB1 antagonist, HMGB1 A box protein was injected into the model mice resulting from TC-1 cell transplantation. Anti-tumor test, immunological influence observation and tumor associated signaling molecules test were carried out with ecombinant adenovirus vector-based human papillomavirus-16 vaccination. RESULTS A box and vaccine combinating injection could decrease the serum HMGB1 level and inhibit NF-?B m RNA expression in model mice, accompanied with a lower tumor occurrence. It also regulated Th1/Th2 type cytokines balance by inducing IFN-? and decreasing IL-4. And compared with model control group, HMGB1 inhibiting made the vaccine played a better performance in reducing NF-?B, Bcl-2, c-IAP2, VEGF, MMP-9 expression and increasing Bax expression in tumor model mice. CONCLUSION HMGB1 can block the immune response and anti-tumor effect of recombinant adenovirus vector-based human papillomavirus-16 vaccine in mouse model, and it probably resulted from HMGB1 playing an important role in cell apoptosis, tumor invasion and metastasis and immune balance regulation.
作者
陈刚
李剑波
高孟
高丽美
吴洁
姜云水
庄昉成
CHEN Gang LI Jianbo GAO Meng GAO Limei WU Jie JIANG Yunshui ZHUANG Fangcheng(Institute of Viral Diseases, Zhejiang Academy of Medical Sciences, Hangzhou 310053, China)
出处
《中国现代应用药学》
CAS
CSCD
2017年第6期827-831,共5页
Chinese Journal of Modern Applied Pharmacy
基金
浙江省自然科学基金项目(LY14C080001)