腺苷对肺癌脑转移的影响及其可能机制  

Effects of adenosine on brain metastasis of lung cancer and its possible mechanism

作　　者：唐明科 魏殿芳 刘洋 张超越 秦丽娟 TANG Ming-ke;WEI Dian-fang;LIU Yang;ZHANG Chao-yue;QIN Li-juan(Department of Physiology,College of Basic Medical Sciences,North China University of Science andTechnology,Tangshan063000,China;Hebei Key Laboratory for Chronic Diseases,Tangshan063000,China)

机构地区：[1]华北理工大学基础医学院生理学教研室,唐山063000 [2]河北省慢性疾病重点实验室,唐山063000

出　　处：《临床与实验病理学杂志》2019年第1期19-22,共4页Chinese Journal of Clinical and Experimental Pathology

基　　金：国家自然科学基金(81101912);河北省高等学校科学技术研究项目(ZD20160082);河北省卫生厅科学研究基金(20170901)

摘　　要：目的探讨腺苷对肺癌脑转移的影响及其可能机制。方法采用Western blot法检测肺癌细胞内缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)和血脑屏障脑微血管内皮细胞上的紧密连接蛋白ZO-1的表达水平;应用ELISA法测定肺癌细胞培养液内腺苷的含量。采用荧光分析法检测体外血脑屏障模型的通透性改变;用Hemocytometer计数Transwell下室的A549肺癌细胞数。结果肺癌细胞中HIF-1的表达和肺癌细胞培养液内腺苷含量均于肺癌细胞缺氧12 h时达最高水平。与此同时,血脑屏障ZO-1蛋白的表达最低,血脑屏障通透性最大(7. 11),透过血脑屏障模型的肺癌细胞数最多(84. 6)。腺苷引起血脑屏障通透性增加,其变化趋势与缺氧肺癌细胞培养液的作用一致。结论缺氧可引起肺癌细胞释放腺苷增多,增多的腺苷导致血脑屏障紧密连接蛋白ZO-1表达减少,导致血脑屏障通透性增大,最终引起肺癌脑转移。Purpose To clarify the effect of adenosine on brain metastasis of lung cancer and the possible mechanism of adenosine promoting brain metastasis of lung cancer.Methods Western blot was used to dynamically detect the expression level of hypoxia inducible factor-1(HIF-1)in lung cancer cells and tight junction protein ZO-1 in brain microvascular endothelial cells on blood-brain barrier.The content of adenosine in lung cancer cell culture was determined by ELISA.Fluorescence analysis was used to detect the changes of permeability of the blood-brain barrier model in vitro.Hemocytometer counts the number of A549 lung cancer cells in Transwell's lower chamber.Results The expression level of HIF-1 in lung cancer cells and the content of adenosine in lung cancer cell culture reached the highest level when lung cancer cells were deprived of oxygen for 12 hours.At the same time,the expression level of ZO-1 protein in the blood-brain barrier was the lowest,the blood-brain barrier permeability was the highest(7.11),and the number of lung cancer cells passing through the blood-brain barrier model was the highest(84.6).The permeability of the blood-brain barrier model increased after the action of adenosine,and its change trend was consistent with the effect of hypoxic lung cancer cell culture solution.Conclusion Hypoxia can induce the lung cancer cell to release adenosine,the increased adenosine can reduce the expression of tight junction protein ZO-1 in blood brain barrier,which leads to the increase of permeability of blood-brain barrier and eventually lead to brain metastasis of lung cancer.

关 键 词：肺肿瘤 脑转移 腺苷 HIF-1 脑微血管内皮细胞 ZO-1蛋白 

分 类 号：R734.2[医药卫生—肿瘤] R739.41[医药卫生—临床医学]