Zhang K, Mack P, Wong K P
Department of Experimental Surgery, BLK 9, Level 2, Singapore General Hospital, Outram Road, Singapore, 169608, Republic of Singapore.
Int J Oncol. 1998 Apr;12(4):871-82. doi: 10.3892/ijo.12.4.871.
Glutathione conjugation and transport of glutathione conjugates of anticancer drugs out of cells have been shown to work as a system in the detoxification of many anticancer drugs. The major components of this system include glutathione (GSH), GSH-related enzymes and glutathione conjugate export pump (GS-X pump). GSH can combine with anticancer drugs to form less toxic and more water soluble GSH conjugates, the conjugation reaction is catalysed by glutathione S-transferases (GSTs). The GSH conjugates of anticancer drugs can be exported from cells by GS-X pump or multidrug resistance-associated protein (MRP). GSH, glutathione-related enzymes and GS-X pump or MRP have been found to be increased or overexpressed in many drug resistant cells. Increased detoxification of anticancer drugs by this system may confer drug resistance. Inhibition of this detoxification system is a strategy for modulation of drug resistance.
谷胱甘肽结合以及抗癌药物的谷胱甘肽结合物从细胞中转运出去，已被证明是许多抗癌药物解毒系统的一部分。该系统的主要组成部分包括谷胱甘肽（GSH）、与GSH相关的酶以及谷胱甘肽结合物输出泵（GS-X泵）。GSH可与抗癌药物结合形成毒性较小且水溶性更强的GSH结合物，结合反应由谷胱甘肽S-转移酶（GSTs）催化。抗癌药物的GSH结合物可通过GS-X泵或多药耐药相关蛋白（MRP）从细胞中输出。已发现GSH、与GSH相关的酶以及GS-X泵或MRP在许多耐药细胞中增加或过度表达。该系统对抗癌药物解毒作用的增强可能导致耐药性。抑制这种解毒系统是调节耐药性的一种策略。
