多药耐药相关蛋白1介导的ATP依赖型溶质转运的分子机制

Molecular mechanism of ATP-dependent solute transport by multidrug resistance-associated protein 1.

作者信息

Chang Xiu-bao

机构信息

Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.

出版信息

Methods Mol Biol. 2010;596:223-49. doi: 10.1007/978-1-60761-416-6_11.

DOI:10.1007/978-1-60761-416-6_11

PMID:19949927

Abstract

Millions of new cancer patients are diagnosed each year and over half of these patients die from this devastating disease. Thus, cancer causes a major public health problem worldwide. Chemotherapy remains the principal mode to treat many metastatic cancers. However, occurrence of cellular multidrug resistance (MDR) prevents efficient killing of cancer cells, leading to chemotherapeutic treatment failure. Over-expression of ATP-binding cassette transporters, such as P-glycoprotein, breast cancer resistance protein and/or multidrug resistance-associated protein 1 (MRP1), confers an acquired MDR due to their capabilities of transporting a broad range of chemically diverse anticancer drugs across the cell membrane barrier. In this review, the molecular mechanism of ATP-dependent solute transport by MRP1 will be addressed.

摘要

每年有数以百万计的新癌症患者被诊断出来，其中超过一半的患者死于这种毁灭性疾病。因此，癌症在全球范围内引发了一个重大的公共卫生问题。化疗仍然是治疗许多转移性癌症的主要方式。然而，细胞多药耐药性（MDR）的出现阻碍了癌细胞的有效杀伤，导致化疗失败。ATP结合盒转运蛋白的过度表达，如P-糖蛋白、乳腺癌耐药蛋白和/或多药耐药相关蛋白1（MRP1）会导致获得性MDR，因为它们能够将多种化学性质不同的抗癌药物转运穿过细胞膜屏障。在这篇综述中，将探讨MRP1介导的ATP依赖性溶质转运的分子机制。