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关于ABC亚家族C成员10(ABCC10)在抗肿瘤药物外排中作用的最新进展。

Recent advances regarding the role of ABC subfamily C member 10 (ABCC10) in the efflux of antitumor drugs.

作者信息

Kathawala Rishil J, Wang Yi-Jun, Ashby Charles R, Chen Zhe-Sheng

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.

出版信息

Chin J Cancer. 2014 May;33(5):223-30. doi: 10.5732/cjc.013.10122. Epub 2013 Oct 9.

Abstract

ABCC10, also known as multidrug-resistant protein 7 (MRP7), is the tenth member of the C subfamily of the ATP-binding cassette (ABC) superfamily. ABCC10 mediates multidrug resistance (MDR) in cancer cells by preventing the intracellular accumulation of certain antitumor drugs. The ABCC10 transporter is a 171-kDa protein that is localized on the basolateral cell membrane. ABCC10 is a broad-specificity transporter of xenobiotics, including antitumor drugs, such as taxanes, epothilone B, vinca alkaloids, and cytarabine, as well as modulators of the estrogen pathway, such as tamoxifen. In recent years, ABCC10 inhibitors, including cepharanthine, lapatinib, erlotinib, nilotinib, imatinib, sildenafil, and vardenafil, have been reported to overcome ABCC10-mediated MDR. This review discusses some recent and clinically relevant aspects of the ABCC10 drug efflux transporter from the perspective of current chemotherapy, particularly its inhibition by tyrosine kinase inhibitors and phosphodiesterase type 5 inhibitors.

摘要

ABCC10,也被称为多药耐药蛋白7(MRP7),是ATP结合盒(ABC)超家族C亚家族的第十个成员。ABCC10通过阻止某些抗肿瘤药物在细胞内蓄积来介导癌细胞的多药耐药(MDR)。ABCC10转运蛋白是一种171 kDa的蛋白质,定位于基底外侧细胞膜。ABCC10是一种对外源性物质具有广泛特异性的转运蛋白,这些外源性物质包括抗肿瘤药物,如紫杉烷类、埃博霉素B、长春花生物碱和阿糖胞苷,以及雌激素途径的调节剂,如他莫昔芬。近年来,已报道包括千金藤素、拉帕替尼、厄洛替尼、尼洛替尼、伊马替尼、西地那非和伐地那非在内的ABCC10抑制剂可克服ABCC10介导的MDR。本综述从当前化疗的角度讨论了ABCC10药物外排转运蛋白的一些近期和临床相关方面,特别是其被酪氨酸激酶抑制剂和5型磷酸二酯酶抑制剂抑制的情况。

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