Sodani Kamlesh, Patel Atish, Kathawala Rishil J, Chen Zhe-Sheng
Department of Pharmaceutical Sciences, St. John's University, Queens, NY 11439, USA.
Chin J Cancer. 2012 Feb;31(2):58-72. doi: 10.5732/cjc.011.10329. Epub 2011 Nov 18.
Multidrug resistance proteins (MRPs) are members of the C family of a group of proteins named ATP-binding cassette (ABC) transporters. These ABC transporters together form the largest branch of proteins within the human body. The MRP family comprises of 13 members, of which MRP1 to MRP9 are the major transporters indicated to cause multidrug resistance in tumor cells by extruding anticancer drugs out of the cell. They are mainly lipophilic anionic transporters and are reported to transport free or conjugates of glutathione (GSH), glucuronate, or sulphate. In addition, MRP1 to MRP3 can transport neutral organic drugs in free form in the presence of free GSH. Collectively, MRPs can transport drugs that differ structurally and mechanistically, including natural anticancer drugs, nucleoside analogs, antimetabolites, and tyrosine kinase inhibitors. Many of these MRPs transport physiologically important anions such as leukotriene C4, bilirubin glucuronide, and cyclic nucleotides. This review focuses mainly on the physiological functions, cellular resistance characteristics, and probable in vivo role of MRP1 to MRP9.
多药耐药蛋白（MRPs）是一组名为ATP结合盒（ABC）转运蛋白的C家族成员。这些ABC转运蛋白共同构成了人体内最大的蛋白质分支。MRP家族由13个成员组成，其中MRP1至MRP9是主要的转运蛋白，它们通过将抗癌药物排出细胞外而导致肿瘤细胞产生多药耐药性。它们主要是亲脂性阴离子转运蛋白，据报道可转运谷胱甘肽（GSH）、葡萄糖醛酸或硫酸盐的游离形式或结合物。此外，在游离GSH存在的情况下，MRP1至MRP3可以以游离形式转运中性有机药物。总的来说，MRPs可以转运结构和机制不同的药物，包括天然抗癌药物、核苷类似物、抗代谢物和酪氨酸激酶抑制剂。许多这些MRPs还转运生理上重要的阴离子，如白三烯C4、胆红素葡萄糖醛酸和环核苷酸。本综述主要关注MRP1至MRP9的生理功能、细胞耐药特性以及在体内可能发挥的作用。
