铜诱导肿瘤细胞死亡机制及其在肿瘤治疗中的研究进展

The mechanism of copper-induced tumor cell death and its research progress in cancer therapy

铜是人体必不可少的微量元素之一,在多种基本生物学功能中起着关键作用,并且受到铜伴侣蛋白及铜转运蛋白的严格调控。铜在肿瘤生长、上皮-间充质转化、肿瘤微环境和转移前生态位的形成中发挥重要作用,因此铜稳态的失衡可影响肿瘤细胞的生长,导致细胞死亡。铜可通过多种方式诱导肿瘤细胞死亡,如诱导活性氧催化氧化应激、抑制泛素-蛋白酶体系统、肿瘤血管的生成受到抑制等,而新近发现的一种新的调节性细胞死亡方式即“铜死亡”与以往已知的细胞死亡机制都有所不同。因此,铜诱导的调节性细胞死亡机制引起了人们的极大关注,并成为肿瘤治疗领域的研究热点。论文综述铜诱导肿瘤细胞死亡机制的研究进展,并回顾铜诱导肿瘤细胞死亡在乳腺癌、结直肠癌、肺癌、前列腺癌等各种肿瘤治疗中的研究进展。

Copper is an essential trace element in the human body that plays a key role in several basic biological functions.The safe and specific transport of copper is regulated by copper chaperones and copper transporters.Copper plays an important role in tumor growth,epithelial-mesenchymal transition,tumor microenvironment and pre-metastatic niche formation.Disruption of copper homeostasis alters tumor cell growth and leads to cell death.Copper can induce tumor cell death in several ways,such as reactive oxygen species accumulation,proteasome inhibition,and antiangiogenesis.A new form of copper-induced regulated cell death,called “cuprotosis,” differs from previously known cell death mechanisms and has become a research hotspot in the field of tumor therapy.In this paper,recent research on the mechanism of copper-induced tumor cell death is introduced,and recent research of copper-induced tumor cell death in the treatment of breast,colorectal,lung,and prostate cancers is reviewed.