基于微流控芯片仿生肺癌模型的STC-1 在肺癌转移过程中的作用研究

Lung cancer metastasis is closely related to the tumor microenvironment. To confirm the molecular mechanisms of lung cancer metastasis impacting on microenvironment, will cut off the underlying pathways which involved in the improvement of seeds on the soil and thus may provide a novel therapeutic target for lung cancer patients. The complexity of the molecular mechanisms network, the limitations of existing research technology, making mechanism of lung cancer metastasis remains unclear. In our previous study, we used proteomic analysis to select a possible key molecule in lung cancer metastasis STC-1. Combined with bioinformatics analysis, the STC-1 may activate the PI3K /AKT signaling pathway in lung cancer cells to induce epithelial-mesenchymal transition, and promote lung cancer metastasis. At the same time, we have successfully constructed microfluidic bionic lung cancer model, to reproduce the pathological process of metastasis, and to achieve dynamic monitoring for a variety of indicators. Based on the previous study, this project plans to dynamically monitored STC-1/PI3K/AKT pathway and EMT associated proteins changes on bionic chip platform, conventional in vitro platforms, and in vivo animal model. Clarify the role of STC-1 in lung cancer metastasis, in order to provide key targets for lung cancer. The verification about reliability of the results in bionic chip will provide a new research platform for the study of lung cancer metastasis.

肺癌转移与微环境密切相关。明确肺癌细胞与微环境相互影响的分子机制，将有可能切断种子改造土壤的路径，为肺癌患者提供新的治疗靶点。分子机制网络的复杂性、现有研究手段难以模拟体内微环境的局限性，使得肺癌转移的机制仍不清楚。项目申请人前期研究已利用蛋白质组学技术筛选出肺癌转移中可能的关键分子STC-1，结合生物信息学分析，提出STC-1可能激活PI3K/AKT信号通路诱导肺癌细胞上皮细胞间质转化，从而促进肺癌转移的假说；同时，已成功构建了微流控芯片仿生肺癌模型，再现肺癌转移的病理过程，实现多种指标的动态监测。在此基础上，本项目拟通过芯片仿生平台、体外常规平台、体内动物模型联合检测肺癌转移过程中STC-1/PI3K/AKT信号通路及EMT相关蛋白的表达变化，明确STC-1在肺癌转移过程中的作用，为肺癌治疗提供新的靶点；验证芯片仿生平台结果的可靠性，为肺癌转移机制研究提供了一种新的技术手段。