基于miRNAs芯片分析方法的天然查耳酮体内肺癌化学预防作用和机制研究

肺癌的化学预防是控制肺癌发病趋势提高治疗效果的最佳途径。已报道的天然来源的肺癌化学预防剂多存在体内活性不理想或毒性大、作用机制不明确等问题。我们前期从多种天然药物中垂钓出了具有显著体外肺癌化学预防作用的天然查耳酮。为了进一步评价其体内肺癌预防效果并阐明其作用机制，本课题拟利用miRNAs 芯片分析锁定肺癌启动的关键性miRNAs，以其表达量变化评价天然查耳酮的体内肺癌预防作用。进一步阐明天然查耳酮通过调控miRNAs表达，激活Keap1-Nrf2/ARE信号通路，上调Nrf2蛋白, 从而发挥癌症化学预防作用的机制。本研究首次以肺癌启动关键miRNAs为切入点，明确天然查耳酮的体内肺癌预防作用与机制，这些关键miRNAs将成为肺癌化学预防的新靶点。实验中建立起来的肺癌化学预防体内评价模型首次将三种评价方式引入到一个体系中，药物用量少、周期短、检测灵敏，适合于天然产物体内肺癌预防作用的快速评价

Chemoprevention is the best strategy to control the increasing tendency and improve the therapy effect of lung cancer. Some difficulties, including desirable effect in vivo, toxicity and undefined mechanism, still exist in research on the lung cancer chemoprevention agents. In our previous work, we have found out some natural chalcones with significant chemoprevention activity in vitro. Now we want to focus on the key miRNAs for lung cancer to evaluate the cancer chemoprevention effect of natural chalcone in vivo by means of miRNAs array analysis. Furthermore, it will be clarified that the natural chalcone could regulate the key miRNAs, which can activate Keap1-Nrf2/ARE signal pathway and up-regulate Nrf2. It is the first time to explore the lung cancer chemoprevention effect of natural chalcone based on the key miRNAs for early lung cancer. These key miRNAs are expected to become new target of lung cancer chemoprevention. The animal model used in our work employed traditional anatomical pathology, imaging features and molecular pathology firstly. It is a good method for fast assay of chemoprevention effect of natural product.