恩度联合放疗对胃癌移植瘤小鼠肿瘤微环境的影响  

EFFECTS OF ENDOSTAR COMBINED WITH RADIOTHERAPY ON TUMOR MICROENVIRONMENT OF GASTRIC CANCERTRANSPLANTED MICE

作　　者：吴海英[1] 魏鑫 王海冀[1] 周丹丹[1] 陆海军[1] 

机构地区：[1]青岛大学附属医院肿瘤科,山东青岛266003 [2]日照市岚山区人民医院

出　　处：《齐鲁医学杂志》2016年第2期138-141,144,共5页Medical Journal of Qilu

摘　　要：目的探讨重组人内皮抑素（恩度）联合放疗对胃癌移植瘤小鼠肿瘤免疫微环境的影响及其作用机制。方法制备32只胃癌移植瘤小鼠模型,随机分为空白对照组、恩度组、放疗组、恩度联合放疗组,分别给予相应处理。于第14天开始,每隔2d检测各组小鼠移植瘤的最大直径与最小直径,计算肿瘤体积并求其平均值,绘制肿瘤生长曲线,计算抑瘤率。于种瘤28d后处死小鼠,采用流式细胞术检测荷瘤小鼠肿瘤组织中髓源抑制性细胞（MDSC）、Foxp3调节性T细胞（TregFoxp3）比例;ELISA法检测肿瘤组织白细胞介素-10（IL-10）、转化生长因子-β1（TGF-β1）的表达水平。结果恩度组、放疗组、恩度联合放疗组肿瘤体积增长速度及大小均小于对照组,其中恩度联合放疗组肿瘤体积增长最慢且体积最小,抑瘤率最高;析因设计的方差分析结果显示,恩度联合放疗在抑制肿瘤生长,降低IL-10、TGF-β1含量以及降低MDSC、TregFoxp3所占比例方面存在交互作用且为正效应（F=4.91~5.72,P〈0.05）,即恩度与放疗之间存在协同作用。当固定使用或不使用放疗时,使用恩度组较不使用恩度组移植瘤质量下降,IL-10、TGF-β1含量以及MDSC、TregFoxp3所占比例降低（F=5.36~6.97,P〈0.05）;当固定使用或不使用恩度时,使用放疗较不使用放疗移植瘤质量下降,IL-10、TGF-β1含量以及MDSC、TregFoxp3所占比例降低,差异均有统计学意义（F=4.27~6.95,P〈0.05）。结论恩度联合放疗可以通过协同作用降低肿瘤微环境中的免疫抑制作用,从而更加明显地抑制肿瘤生长。Objective To explore the effect and its mechanism of endostar combined with radiotherapy on immune micro- environment of gastric cancer-transplanted mice. Methods A gastric cancer-transplanted model in 32 mice was created and even- ly divided into four groups in random as control group,endostar （ES） group, radiotherapy （RT） group and ES＋RT group. Corre- sponding handling was offered. Starting from the 14th day, the maximal diameter and minimal diameter of the transplated tumors in each group were measured every 2 d, the gross tumor volume and its mean value were calculated. The curve of tumor growth was drawed, and tumor inhibition rate calculated. On day 28, all the experimental mice were sacrificed. The proportion of MDSC and TregFoxp3 in tumor tissue was detected with flow eytometry, and the expressions of IL-1 and TGF-β1 in tumor tissue were de- tected using ELISA. Results The velocity and size of tumor growth in ES, RT and ES＋RT groups were all less than that in the control group, in which, the size of the tumor was smallest, the velocity was the slowest, and tumor inhibition rate was the hi- ghest in ES＋RT group. The results of variance analysis showed that in regard to inhibiting tumor growth, reducing IL-10 and TGF-β1 contents, and proportion of MDSC and TregFoxp3, there was synergistic effect between endostar combined with radiothe- rapy （F=4.91--5.72,P〈0.05）. When radiotherapy was used regularly or not used at all, the weight of transplanted tumor de- creased in the group that used endostar, the contents of IL-10 and TGF-β1, and the proportion of MDSC and TregFoxp3 reduced as well compared with the group that did not use endostar （F=5.36--6.97,P〈0.05）. When endostar was used regularly or not used at all, the use of radiotherapy reduced the weight of transplanted tumor and contents of IL-10 and TGF-β1, as well as proportion of MDSC and TregFoxp3 versus that did not use radiotherapy, the differences being statistically significant （F = 4.27- 6.95, P〈0.05）. Conclusion En

关 键 词：血管生成抑制剂 胃肿瘤 放射疗法 肿瘤微环境 

分 类 号：R735.2[医药卫生—肿瘤]