高迁移率族蛋白B1对激素难治性前列腺癌冷冻免疫反应的影响  

The effect of high mobility group protein B1 on cryoimmunologic reaction in hormone-refractory prostate cancer: an experimental study in rats

作　　者：刘长富[1] 郭志[1] 司同国[1] 邢文阁[1] 刘方[1] 于海鹏[1] 

机构地区：[1]天津医科大学附属肿瘤医院介入治疗科天津市肿瘤防治重点试验室,300060

出　　处：《介入放射学杂志》2013年第6期494-497,共4页Journal of Interventional Radiology

基　　金：国家自然基金资助项目(81001002);天津市卫生局科技基金资助项目(2010KZ71)

摘　　要：目的探讨高迁移率族蛋白B1(high mobility group protein B1,HMGB1)对激素难治性前列腺癌冷冻免疫反应的影响。方法复制RM-1细胞激素非依赖性前列腺癌模型,将50只小鼠随机分为对照组(n=25)和冷冻消融治疗组(n=25)。利用氩氦冷冻系统针式冷冻器行皮下移植瘤冷冻消融治疗。分别于冷冻消融治疗前、治疗后1、7、14、21 d应用Western印迹技术检测HMGB1蛋白在肿瘤局部的表达情况,应用流式细胞术检测肿瘤局部树突状细胞(DC)的数量及活化比例。结果治疗组肿瘤局部HMGB1表达水平及DC数量及活化比例均于术后第7天达最高值,与术前相比差异有统计学意义(P<0.05);对照组HMGB1表达水平及DC数量及活化比例无明显改变,组内比较差异无统计学意义(P>0.05)。治疗组术后1、7、14 d,肿瘤局部HMGB1表达水平及DC数量及活化比例均高于对照组,组间差异有统计学意义(P<0.05)。相关性分析显示,治疗组肿瘤局部HMGB1表达量与DC数量、DC活化比例均呈高度正相关(r=0.883,r=0.997,P<0.05)。结论冷冻消融治疗导致肿瘤细胞坏死的同时可释放大量HMGB1,这些释放至细胞外的HMGB1在冷冻消融治疗后刺激机体产生特异性抗肿瘤冷冻免疫反应中发挥重要作用。Objective To investigate the impact of high mobility group protein B1 （HGMB1） on cryoimmunology response in hormone-refractory prostate cancer （HRPC）. Methods Mouse models of HRPC were established by subcutaneous injection of RM- 1 prostate cancer cells, and a total of 50 tumor-bearing mice were randomly divided into control group （n = 25）and cryoablation group （n = 25）. Cryoablation was applied to the tumor lesion through cryosurgery needle with 1.7mm diameter by using Endocare Argon-Helium cryosurgery system （AHCS）. The number and maturation changes of dendritic cell （DC） in tumor were assessed by flow cytometry and the levels of HMGB1 in tumor tissues were determined by Western blot technology one day before cryosurgery as well as one, 7, 14 and 21 days after cryosurgery separately. Results In cryoablation group, the levels of HMGB1 as well as the number and maturation of DC in tumor tissues reached their highest peaks in the 7th day after AHCS, and compared with the levels determined before treatment the differences were statistically significant （P 〈 0.05）. However, in control group no significant differences in the levels of HMGBI as well as in the number and maturation of DC in tumor tissuesexisted between preoperative data and post operative ones （P 〉 0.05）. The levels of HMGB1 as well as the number and maturation changes of DC in tumor tissues determined at one, 7 and 14 days after cryosurgery in cryoablation group were significantly higher than those in control group（P 〈 0.05）. Correlation analysis showed that the expression levels of HMGB1 had a parallel relationship with the number of DC （r = 0.883, P 〈 0.05） as well as with the maturation changes of DC （r = 0.997, P 〈 0.05） in the cryoablation group. Conclusion Cryoablation therapy can make the tumor cells release large amount of HMGB1 in association with tumor cell necrosis. And the released extracellular HMGB1 plays an important role in stimulating the body to produce the tumor-specific immune r

关 键 词：前列腺癌 冷冻消融 高迁移族蛋白B-1 树突状细胞 

分 类 号：R737.25[医药卫生—肿瘤]