基底拓扑和硬度对胶质瘤耐药性的调控作用及机制

The the physical and mechanical factors of mechanical microenvironment in the tumor not only directly affect the function of the cells, but also affect the ability of the cells to sensate the surrounding signal molecules. Glioma is the most common primary tumor of the central nervous system. Due to the special growth and infiltration of the growth mode, primary and secondary resistance more, the mortality rate of glioma patients is very high. And the inherent mechanical environment of glioma cells in vivo survival environment is one of the factors that could not be ignored in the drug resistance of glioma. It is very important to study the mechanism of glioma cells to understand the specific mechanical environment of brain tissue, and to study the mechanism of drug resistance. The purpose of this project is to use micro / nano mode technology to achieve the growth of glioma cells on the very soft of the matrix, to study glioma cells on different stiffness and collagen formation of micro / nano-topological, to understand the regulation of drug resistance and related molecular regulation mechanism. Finally, clarify the relationship between drug resistance and mechanical response of glioma cells to provide new theoretical basis and treatment reference.

细胞微环境由各种细胞、细胞外基质、生化分子等组成。细胞外基质的物理力学性质和各种生化分子不仅维持着细胞和组织的正常功能，并且这些因素微小的改变也同样影响细胞的生理改变，进而影响疾病的发展。肿瘤微环境中细胞外基质的拓扑结构和硬度影响肿瘤细胞感受周围信号分子的能力，同时影响肿瘤细胞对药物的耐药性，但肿瘤细胞感受基底应力引起耐药性的机理至今尚不清楚。本研究以中枢神经系统最常见的原发肿瘤胶质瘤为研究对象，模拟胶质瘤生长的各种硬度和拓扑结构形成的力学微环境，尝试研究二者对胶质瘤细胞如何感受脑组织的特殊力学环境变化导致耐药性的机制。本项目拟运用微/纳米模式化技术在硬度较低的基质上实现胶质瘤细胞的模式化生长，在此基础上研究硬度和拓扑结构(包括模式化的拓扑结构和胶原交联形成的微拓扑结构)耦合的基底对胶质瘤细胞的耐药作用及相关分子调控机制，为阐明胶质瘤耐药性与力学响应的关系提供新的实验数据和理论依据。