Molecular mechanisms of cisplatin resistance
Molecular mechanisms of cisplatin resistance
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DOI：
10.1360/032013-305
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发表时间：
2014-03
期刊：
影响因子：
--
通讯作者：
Zhaoyong Xi;Yangzhong Liu
中科院分区：
文献类型：
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作者：
Zhaoyong Xi;Yangzhong Liu
顺铂广泛用于多种类型实体瘤的临床治疗。顺铂的细胞毒性主要通过其与DNA的结合介导，随后是DNA损伤反应和细胞凋亡的诱导。然而，以顺铂为基础的化疗往往受到内在或获得性耐药的限制。在过去的30年里，人们对顺铂耐药进行了深入的研究，并对顺铂耐药的分子机制有了很大的了解。顺铂耐药有多种机制，并且耐药过程似乎是多因素的。本文就顺铂在细胞内蓄积减少、药物解毒作用增强、DNA修复和损伤反应、细胞凋亡途径的改变以及间接信号通路的改变等机制进行了系统的阐述和讨论。
Cisplatin is widely used in the clinical treatment of many types of solid tumors. The cytotoxicity of cisplatin is primarily mediated by its binding to DNA followed by the DNA damage response and the induction of apoptosis. However, the cisplatin-based chemotherapy is often limited by the intrinsic or acquired drug resistance. During the past 30 years, intense researches have been conducted on the cisplatin resistance and the understanding about the molecular mechanisms has largely arisen. There are several mechanisms responsible for cisplatin resistance and the process of the drug resistance appears to be multifactorial. In this review, we systematically describe and discuss these mechanisms, including the reduced intracellular accumulation of cisplatin, the increased drug detoxification, the alterations in DNA repair and DNA damage response and apoptosis pathways as well as the changes of indirect signal pathways.