清热解毒法抑制非小细胞肺癌化疗期间上皮间质转化的机制研究

Epithelial mesenchymal transition (EMT) is the most critical factor led to non-small cell lung cancer (NSCLC) transfer, resistance and eventually led to the death. Inhibition of EMT activation signal conduction in tumor cells has become an important strategy in the treatment of non-small cell lung cancer. Treatment of law and evidence-based medicine, Meta-analysis results for Qingrejiedu drugs to treat non-small cell lung cancer show that the Qingrejiedu method can effectively inhibit NSCLC's epithelial mesenchymal transformation.during chemotherapy. However, its mechanism of action and means is not clear. On the basis of the preliminary study , Innovatively our group use PET-CT technology,real-time, dynamic, accurately,to detect the drug's intervention effect of the NSCLC epithelial -mesenchymal transformation. And base on the database of the regulatory proteins target - drug molecules of epithelial mesenchymal transition , with a molecular docking ,we screen the Qingrejiedu method's interventing targets in the role of epithelial mesenchymal transition. And then by immunohistochemistry, Western blot and real-time PCR experiments to validate the targets and means in controling the EMT for Qingrejiedu method from the nucleic acid and protein levels. The results provide experimental evidence for the clinical application of Chinese medicine treatment of NSCLC, and further theoretical support from a new perspective, and has important scientific significance and potential applications.

上皮间质转化（EMT）是非小细胞肺癌（NSCLC）出现转移、耐药最终导致患者死亡最重要的原因，抑制肿瘤细胞的上皮间质转化及EMT的信号传导通路是治疗非小细胞肺癌的重要策略。清热解毒法是中医肿瘤的重要法则.在治疗非小细胞肺癌的疗效的证治规律和循证医学的Meta分析表明清热解毒法能有效抑制NSCLC化疗期间出现的上皮间质转化,但其作用机制不明。课题组在已经构建上皮间质转化调控蛋白靶标-药物分子数据库的基础上，借助分子对接技术筛选出清热解毒法对上皮间质转化干预作用的靶点，采用PET-CT技术结合免疫组化、Western blot和real-time PCR等实验方法，实时、动态、精确的检测药物对NSCLC上皮间质转化的干预作用,从核酸、蛋白水平验证研究清热解毒法调控EMT的靶点和信号通路。为应用清热解毒法治疗NSCLC提供实验证据和理论支持，具有重要的科学价值和临床指导意义。

上皮间质转化（EMT）是非小细胞肺癌（NSCLC）出现转移、耐药最终导致死亡的最关键因素，抑制EMT激活信号在肿瘤细胞内的传导已成为治疗非小细胞肺癌的重要策略。治疗非小细胞肺癌疗效的证治规律和循证医学的Meta分析结果表明清热解毒法能有效抑制NSCLC化疗期间出现的上皮间质转化，但其作用机制和途径不明确。.课题组运用化学信息学方法，选择了木犀草素、冬凌草甲素、熊果酸等共性成分母核进行研究。通过实验研究发现清热解毒药及其代表性成分可以有效抑制非小细胞肺癌的上皮间质转化。并且清热解毒药代表性成分对肿瘤转移的抑制作用和肿瘤转移过程中上皮间质转化的程度有着密切的相关性。.课题组在构建上皮间质转化调控蛋白靶标-药物分子数据库基础上，借助分子对接技术筛选共性成分对上皮间质转化干预作用的靶点，再通过分子生物学实验方法，研究验证其调控EMT的靶点和途径。.研究结果部分解释了肿瘤转移过程中EMT的不同阶段应用清热解毒法其治疗作用的差异，从新的视角为临床应用中药治疗NSCLC提供实验证据和进一步的理论支持，具有重要的科学意义和广阔的应用前景。