IL-17A通过增强肿瘤血管生成和侵袭促进肿瘤发展  

IL-17A promotes tumor growth through enhancing tumor angiogenesis and invasiveness

作　　者：石宝玉[1] 周灵[1] 朱海星[1] 万欢英[1] 时国朝[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院呼吸科,200025

出　　处：《国际呼吸杂志》2014年第14期1075-1080,共6页International Journal of Respiration

基　　金：国家自然基金资助项目（81270083）;上海交通大学医工交叉基金资助项目（YG2011MS44）

摘　　要：目的探讨IL-17A在非小细胞肺癌血管形成和侵袭中的作用。方法Lewis肺癌细胞（LLC）在不同浓度IL-17A（0、25、50、100和200μg／L）条件下行增殖实验，LLC在50μg／L IL-17A和0μg／LIL-17A刺激下行侵袭实验。LLC在IL-17A刺激不同时间点下用实时定量PCR（RT—PCR）测定血管内皮生长因子-A（VEGF—A）、血管生成素-2（Ang-2）、基质金属蛋白酶-2（MMP-2）、MMP-9mRNA表达。C57BL／6小鼠接种LLC后随机分为3组，每组6只，分别予以瘤内注射PBS、对照腺病毒（Ad—NC）和干扰腺病毒（Ad—si—IL-17a，IL-17a基因沉默），16d后处死小鼠，提取肿瘤组织RNA，RT-PCR检测VEGF-A、Ang-2、MMP-2和MMP-9mRNA表达。结果体外培养条件下IL-17A对肿瘤细胞的增殖能力没有影响，与无IL-17A组相比，50μg／L浓度的IL-17A组的肿瘤细胞VEGF-A、Ang-2、MMP-2和MMP-9mRNA表达水平明显升高，且肿瘤细胞侵袭能力增强（P〈0．01）。Ad—si—IL-17a组小鼠在13d（P〈0．05）和16d（P〈0．01）时肿瘤明显小于Ad-NC组和PBS组。Ad-si-IL-17a组肿瘤VEGF-A、Ang-2、MMP-2和MMP-9ITIRNA表达水平低于Ad—NC组和PBS组。结论靶向IL-17A的治疗可能为肿瘤治疗提供新思路。Objective To explore the role of interleukin-17A （IL-17A） in angiogenesis and invasiveness of mouse non-small cell lung cancer. Methods The proliferation ability of LLC was testedusing CCK-8 kit in the presence of different concentrations of IL-17A （0, 25, 50, 100, 200 μg/L）. Invasiveness of LLC in the presence or absence of 50 μg/L IL-17A was measured. Using RT-PCR,expressions of vascular endothelial growth factor-A （ VEGF-A ）, angiopoietin-2 （ Ang-2 ）, matrix metalloproteinase-2 （MMP-2） ,and MMP-9 mRNA at different time points in the presence of IL-17A weremeasured. LLC was injected in mice subcutaneously and mice were randomly divided into three groups. Each group contained six miee. PBS,Ad-NC or Ad-si-IL-17a were injected intratumorally and mice weresacrificed for tumor RNA at 16d. By the means of RT-PCR, expressions of VEGF-A, Ang-2, MMP-2, and MMP-9 mRNA were measured in different groups. Results It was shown that IL-17A could not promotetumor cell growth in vitro,but enhanced the invasiveness of tumor ceil （ P 〈0.01） ,and could increase the expressions of VEGF-A, Ang-2, MMP-2, and MMP-9 mRNA. In vivo, LLC tumor growth was inhibitedby intratumoral injection of adenovirus encoding si-IL-17a at 13d （ P 〈0.05） and 16d （ P 〈0.01）. The expressions of VEGF-A, Ang-2, MMP-2, and MMP 9 mRNA in Ad-si-IL-17a group were lower than thosein other two groups. Conclusions The blocking of IL-17A may be new strategy for treatment of cancer.

关 键 词：肿瘤 免疫 白介素17A 血管生成 侵袭 

分 类 号：R734.2[医药卫生—肿瘤]