表阿霉素是乳腺癌的基本化疗药物，但肿瘤细胞对其产生的继发性耐药严重影响临床疗效和患者预后。关于表阿霉素耐药机制的研究已取得某些进展，但远未清晰。自噬是一种真核细胞蛋白降解机制，在不同的条件下，既有细胞保护作用，又可以导致细胞发生自噬性死亡。最近研究结果提示，自噬可能是一种潜在的化疗耐药机制，但关于此方面研究报道较少，尤其通过耐药细胞直接的研究更少。Ambra1是一种促自噬因子，其在细胞内表达水平及亚细胞定位的改变是决定细胞进入自噬或凋亡的重要因素，可能在化疗耐药中具有一定作用。本项目将在我们前期研究的基础上，通过诱导的多个对表阿霉素耐药的细胞株，深入的研究自噬与表阿霉素耐药之间的关系；并通过检测细胞内Ambra1表达及亚细胞定位的变化，揭示自噬参与乳腺癌对表阿霉素耐药发生的分子机制。通过本项目研究有助于进一步理解表阿霉素作用机理和耐药机制，为制定增强肿瘤对表阿霉素敏感性新策略提供理论依据。

Epirubicin (EPI) is one of the most effective drugs against breast cancer, while the acquired resistance of cancer cells to EPI is becoming a major obstacle for successful cancer therapy. Although some progress has been made in EPI-resistance, it is still not very clear. Macroautophagy (here referred to as autophagy), an evolutionarily conserved lysosome-dependent cellular catabolic degradation, may protect cells from death or lead to autophagic cell death, under different conditions. Recently, it was suggested, according to the results of a series of studies, that autophagy might be a potential mechnism of anti-cancer drug resistance. However, the relationship between autophagy and drug resistance has yet to be defined. Ambra1 is a prompting factor of autophagy. The expression level and subcellular location of Ambra1 will determin the fate of cell. It might have a role in the development of EPI-resistance, which needs study to confirm. On the basis of our previous study, the relationship and molecular mechnism between autophagy and EPI-resistance will be continued to study in diverse induced EPI-resistant cell lines, in this project. The study will be helpful to further understand the mechnism of EPI anti-cancer and resistance. And it might provide a new strategies for us to enhance the sensitivity of breast cancer to EPI.