SO2暴露诱导肺癌肿瘤转移效应及其上皮间质转化（EMT）调控机制

项目名称： SO2暴露诱导肺癌肿瘤转移效应及其上皮间质转化（EMT）调控机制

项目编号： No.21307079

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 环境科学、安全科学

项目作者： 云洋

作者单位： 山西大学

项目金额： 25万元

中文摘要： 肺癌是全球发病率和死亡率最高的恶性肿瘤疾病。流行病学研究表明，SO2吸入与肺癌病死率增加显著相关，而与肺癌发病风险的相关性研究结果仍存有争议，相关分子机制更是鲜见报道。EMT在肺癌肿瘤转移中发挥重要作用。为此，本研究拟通过分别对人正常支气管上皮细胞和肺癌细胞进行SO2衍生物染毒，考察染毒前后自由基水平，转录因子活化，DNA甲基化及EMT标志因子表达的变化，探讨SO2暴露对肺癌早期肿瘤转移和发展的影响，明确EMT发生作为该肿瘤效应早期诊断的生物学标志的可能性，揭示SO2暴露诱导肺癌肿瘤侵袭转移的调控机制；在此基础上拟对肺癌模型小鼠进行SO2动式吸入染毒，进一步验证SO2吸入暴露对肺癌肿瘤远端转移能力的影响及其调控机制。通过本研究，旨在阐明SO2暴露对肺癌肿瘤发展的影响，建立早期诊断分子生物标志，确定EMT发生的调控机制，为健康人群的日常防护和高危人群的临床诊断、治疗和预后提供理论依据。

中文关键词： 二氧化硫；大气细颗粒物；多环芳烃；癌细胞转移；上皮间质转化

英文摘要： Lung cancer is the most common cause of cancer-related mortality in the world.Epidemiologic studies show an association between the mortality of lung cancer and SO2 exposure. However, if SO2 exposure will influence the incidence of lung cancer remains disputed, existing experimental studies also lack evidences as to the presence of effects about SO2. Epithelial-mesenchymal transition (EMT) is considered to be a critical event in the pathogenesis of tumor metastasis. In the present project,we will treat human bronchial epithelial cells and lung cancer cells with SO2 derivatives (bisulfite and sulfite, 3:1 M/M), and examine the changes of ROS generation, transcriptional factors activation, DNA methylation and EMT markers expression to explore the effects of SO2 inhalation on the early tumor metastasis and caner development. Following this, we plan to treat tumor model mices with SO2 at various concentrations and determine the changes of above factors to verify the regulation mechanisms of EMT during SO2 inhalation-caused tumor distant metastasis. The work is undertaken to indicate the effects of SO2 exposure on the process of lung cancer development, illuminate regulation mechanism of the EMT, set up effective biomarkers for early detection, provide experimental evidence for effective protection, early diagnosis a

英文关键词： SO2；PM；PAHS；tumor metastasis；EMT