多药耐药性是肿瘤化疗失败的主要原因，基质刚度作为肿瘤微环境的物理因素之一，探究其与耐药性关系显得尤为重要和迫切。传统的2D细胞培养无法真实模拟肿瘤细胞的真实微环境，使得细胞基本形态及生物学功能受到限制或减弱，无法构建有效的肿瘤生物学模型。本项目以乳腺癌为研究对象，旨在通过构建3D水凝胶仿生细胞外基质力学微环境，模拟体内乳腺癌不同阶段的组织刚度特征，探究基质刚度的变化对于乳腺癌细胞耐药性的影响及其影响机制。通过免疫荧光、活细胞影像和3D细胞力学分析等技术，重点分析FAK-YAP/TAZ信号轴在调控肿瘤耐药性的力学生物学机制。研究结果将有助于加深肿瘤微环境力学性质对肿瘤恶性进程和恶性转化影响的理解和认识，为阐明乳腺癌细胞的耐药机制提供新的方向，为未来肿瘤治疗提供新的实验证据和参考信息，并为抗肿瘤药物的开发提供新靶点。

Multidrug resistance is the most important reason for failure of breast cancer chemotherapy. It is especially significant and urgent to explore the relationship between matrix stiffness and multidrug resistance, due to the matrix stiffness is one of the vital physical factors of tumor microenvironment. The basic morphology and biological functions of cells will be limited or weakened under the traditional 2D cell culture, so it is impossible to build an effective biological model of tumor. In this project, we focus on breast cancer, we will construct 3D hydrogels biomimetic ECM dynamic microenvironment with different hardness to simulate the breast cancer tissue stiffness at different phases. We hope to explore the influence of matrix stiffness on the drug resistance of breast cancer cells and its influencing mechanism. The mechanical and biological mechanism of FAK-YAP /TAZ signal axis in regulating tumor drug resistance will be analyzed by immunofluorescence, living cell imaging and 3D cell mechanics analysis. The finding of this project would help us to understand the influence of tumor microenvironmental mechanical properties on malignant progression and transformation, to provide new experimental evidence and reference information for future cancer treatment, and also provide new targets for the development of new anti-tumor drugs.