有机阴离子转运多肽1B3的研究进展

Advances in the study of organic anion transporting polypeptide 1B3

有机阴离子转运多肽1B3(organic anion transporting polypeptide 1B3,OATP1B3)属于溶质转运体(solute carrier,SLC)超家族,主要负责将内、外源物质转运至肝细胞代谢。OATP1B3是肝脏特异性转运体,通常局限性地分布于肝细胞窦状隙侧肝细胞膜上,近期研究发现在前列腺癌、结肠癌、肺癌等肿瘤组织和细胞中也存在着高表达。溶质转运体1B3(SLCO1B3)具有明显的基因多态性,334T>G和699G>A单体型可明显影响OATP1B3的转运活性,从而介导药物-药物相互作用的发生,导致临床用药的个体差异。此外,OATP1B3可通过作用于孕烷X受体(pregnane X receptor,PXR)和组成性雄甾烷受体(constitutive androstane receptor,CAR)等核受体配体的转运,影响体内PXR和CAR的转录活性,从而调控药物代谢酶如细胞色素P450 3A4(CYP3A4)的表达。本文将对OATP1B3近年来的研究进展进行综述。

OATP1B3,a member of SLC superfamily,is specifically expressed on the sinusoidal membrane of hepatocytes and is considered to be important in hepatic drug elimination.The overexpression of OATP1B3 was found recently in tumor tissues such as prostate,colon,and pancreatic tumors.Sequence variations in SLCO1B3 gene,such as SNPs,have been described and a common haplotype consisting of 334TG and 699GA SNPs is related to altered transport characteristics of OATP1B3.OATP1B3 is of relevance to drug metabolism through affecting alteration of hepatic concentration of endo-and xenobiotic compounds that interact with nuclear receptors such as PXR and CAR,and thereby directly alter the extent of target gene transcription,including major CYP isoenzymes such as CYP3A4.This review will provide an overview of substrates and inhibitors of OATP1B3 and subsequently to assess the effect of genetic mutation on transport activity.The studies linking OATP1B3 with cancer clinical outcomes are also discussed in this review.