自噬在抗肿瘤药物毒性中的作用与机制研究进展

Progress of Research on the Role and Mechanism of Autophagy in the Toxicity of Anti-Tumor Drugs

自噬是真核细胞中高度保守的依赖于溶酶体的胞内降解途径,在众多生理病理过程中发挥重要作用。随着对自噬关键基因与信号通路的深入解析,自噬与抗肿瘤药物毒性之间的关系也逐渐被揭示。抗肿瘤药物作为一类毒性和副作用相对较大的药物,在治疗肿瘤的同时常引起其他脏器系统的损伤。在某些抗肿瘤药物毒性中,自噬可作为一种保护机制减少损伤,但持续或过度的自噬激活亦可导致细胞死亡,诱发毒性。综述自噬发生的调控机制、生理病理作用,着重关注其在抗肿瘤药物毒性中的作用与机制,这将增进对自噬在抗肿瘤药物毒性中发挥的作用的全面认识,有助于发现自噬角色转变的关键要素,为抗肿瘤药物毒性的治疗和基于毒性机制的创新药物研发提供新思路与新靶点。

Autophagy,a highly conserved lysosome-dependent intracellular degradation pathway in eukaryotic cells,plays an important role in many physiological and pathological processes of cells.With the in-depth analysis of the key genes and signaling pathways of autophagy,the relationship between autophagy and drug toxicity has been gradually revealed.As a class of drugs with severe toxic and side effects,anti-tumor drugs often cause damage to other organs while treating tumors.Autophagy acts as a protective mechanism to reduce tissue damage in toxicity caused by some anti-tumor drugs,however,persistent or excessive autophagy activation can also lead to cell death and induce toxicity.This article reviews the regulatory mechanism as well as the physiological and pathological effects of autophagy,with particular focus on the role and mechanism of autophagy in toxicity caused by anti-tumor drugs,which will improve our comprehensive understanding of autophagy in anti-tumor drug toxicity,and help to discover the key elements for the shifting of the role of autophagy,in the hope of providing new insights and targets for the treatment of anti-tumor drugs-induced toxicity and the development of innovative drugs based on toxicity mechanism.