The Tumorigenic Roles of the Cellular REDOX Regulatory Systems.
The Tumorigenic Roles of the Cellular REDOX Regulatory Systems.
复制标题
DOI：
10.1155/2016/8413032
复制
发表时间：
2016
影响因子：
--
通讯作者：
Madureira PA
中科院分区：
文献类型：
--
作者：
Castaldo SA;Freitas JR;Conchinha NV;Madureira PA
细胞氧化还原调节系统在维持氧化还原稳态方面发挥着核心作用，这对于细胞完整性、存活和增殖至关重要。迄今为止，大量数据表明，随着肿瘤的发展，癌细胞通常会经历不断增加的氧化应激，上调这些重要的抗氧化系统，以便在这些极端的氧化应激条件下生存、增殖和转移。由于目前临床上使用的大量化疗药物依靠诱导ROS过载或改变ROS质量来杀死肿瘤，因此癌细胞氧化还原适应是常规化疗的重大障碍。在这篇综述中，我们将首先研究导致肿瘤微环境中普遍观察到的氧化应激增强的不同因素。然后，我们将对当前有关主要抗氧化蛋白和系统的文献进行全面评估，这些蛋白和系统已被证明与肿瘤进展和化疗耐药呈正相关。最后我们对常用的诱导ROS的化疗药物进行分析。目前对癌细胞氧化还原适应的了解提出了开发新的、更有效的疗法来治疗这些通常对传统的ROS诱导化疗有抵抗力的肿瘤的问题。
The cellular REDOX regulatory systems play a central role in maintaining REDOX homeostasis that is crucial for cell integrity, survival, and proliferation. To date, a substantial amount of data has demonstrated that cancer cells typically undergo increasing oxidative stress as the tumor develops, upregulating these important antioxidant systems in order to survive, proliferate, and metastasize under these extreme oxidative stress conditions. Since a large number of chemotherapeutic agents currently used in the clinic rely on the induction of ROS overload or change of ROS quality to kill the tumor, the cancer cell REDOX adaptation represents a significant obstacle to conventional chemotherapy. In this review we will first examine the different factors that contribute to the enhanced oxidative stress generally observed within the tumor microenvironment. We will then make a comprehensive assessment of the current literature regarding the main antioxidant proteins and systems that have been shown to be positively associated with tumor progression and chemoresistance. Finally we will make an analysis of commonly used chemotherapeutic drugs that induce ROS. The current knowledge of cancer cell REDOX adaptation raises the issue of developing novel and more effective therapies for these tumors that are usually resistant to conventional ROS inducing chemotherapy.