内质网应激及氧化应激反应与乳腺癌耐药的研究进展

Research Progress on Endoplasmic Reticulum Stress and Oxidative Stress in Breast Cancer

内质网应激(endoplasmic reticulum stress,ERS)和氧化应激是维持细胞稳态的重要机制之一。ERS通过未折叠蛋白反应(unfolded protein response,UPR)信号通路与氧化应激、细胞自噬和细胞凋亡之间存在交互作用,是应激条件下细胞命运决定的重要环节。ERS能促进自噬发生,诱导细胞死亡,在多种实体肿瘤包括乳腺癌演化中扮演重要角色,靶向ERS/UPR有望成为乳腺癌等肿瘤治疗新策略。全文就ERS/UPR及氧化应激信号通路在乳腺癌中的作用及靶向治疗研究进展作一综述。

Endoplasmic reticulum stress(ERS) and the downstream unfolded protein response(UPR)activation are mechanistically responsible for metabolic homeostasis. Activated signaling pathway mediated by ERS/UPR interplays between cellular autophagy,oxidative stress and apoptosis,which contribute to cell fate decision under deteriorated microenvironment. Accumulating evidence indicates that ERS/UPR play a crucial role in cancer development and progression including treatment response in breast cancer;therefore,targeting ERS/UPR signaling or oxidative stress pathway may be a promising strategy for breast cancer treatment. In this review,the mechanism underlying ERS/UPR activation and the interaction of ERS/UPR activation with cell autophagy,oxidative stress and apoptosis,and discuss the potential targeting therapy for ERS/UPR and NRF2/KEAP1 in breast cancer were summrized.