Abstract:
Multidrug resistance protein 7 (MRP7), also known as ATP-binding cassette (ABC) transporter subfamily C10 (ABCC10), is an ABC transporter that was first identified in 2001. ABCC10/MRP7 is a 171 kDa protein located on the basolateral membrane of cells. ABCC10/MRP7 consists of three transmembrane domains and two nucleotide binding domains. It mediates multidrug resistance of tumor cells to a variety of anticancer drugs by increasing drug efflux and results in reducing intracellular drug accumulation. The transport substrates of ABCC10/MRP7 include antineoplastic drugs such as taxanes, vinca alkaloids, and epothilone B, as well as endobiotics such as leukotriene C4 (LTC4) and estradiol 17 β-D-glucuronide. A variety of ABCC10/MRP7 inhibitors, including cepharanthine, imatinib, erlotinib, tariquidar, and sildenafil, can reverse ABCC10/MRP7-mediated MDR. Additionally, the presence or absence of ABCC10/MRP7 is also closely related to renal tubular dysfunction, obesity, and other diseases. In this review, we discuss: 1) Structure and functions of ABCC10/MRP7; 2) Known substrates and inhibitors of ABCC10/MRP7 and their potential therapeutic applications in cancer; and 3) Role of ABCC10/MRP7 in non-cancerous diseases.
摘要:
多药耐药蛋白7(MRP7),也称为ATP结合盒(ABC)转运蛋白亚家族C10(ABCC10),是2001年首次确定的ABC运输机。ABCC10/MRP7是位于细胞基底外侧膜上的171kDa蛋白。ABCC10/MRP7由三个跨膜结构域和两个核苷酸结合结构域组成。它通过增加药物流出来介导肿瘤细胞对多种抗癌药物的多药耐药性,并导致细胞内药物积累减少。ABCC10/MRP7的转运底物包括紫杉烷类等抗肿瘤药物,长春花生物碱,和埃博霉素B,以及内源性物质,例如白三烯C4(LTC4)和雌二醇17β-D-葡糖苷酸。多种ABCC10/MRP7抑制剂,包括西法兰碱,伊马替尼,厄洛替尼,Tariquidar,还有西地那非,可以逆转ABCC10/MRP7介导的MDR。此外,ABCC10/MRP7的存在与否也与肾小管功能障碍密切相关,肥胖,和其他疾病。在这次审查中,我们讨论:1)ABCC10/MRP7的结构和功能;2)ABCC10/MRP7的已知底物和抑制剂及其在癌症中的潜在治疗应用;3)ABCC10/MRP7在非癌症疾病中的作用。