有机阴离子转运多肽(Oatps)在激素依赖性乳腺癌和前列腺癌细胞存活中的作用

T. Nakanishi
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引用次数: 1

摘要

被归类为溶质载体(SLC)转运蛋白超家族的转运蛋白在生物体中对细胞生存所需的营养物质的进口至关重要。在过去的二十年中,越来越多的令人信服的证据表明,SLC转运蛋白与临床重要的抗癌药物相互作用,并有助于其药代动力学,特别是吸收、消除和分布的生物制药过程。此外,许多SLC转运蛋白在癌细胞中表现出差异上调,这可能代表了对改变的营养需求的适应性反应。因此,有可能利用它们作为有效给药的载体,以及作为阻断恶性肿瘤细胞生长必需营养物质的药理靶点。本文将简要介绍识别内源性和外源性有机阴离子化合物的有机阴离子转运多肽及其在癌细胞中上调的最新发现。此外,ooatp介导的类固醇激素硫酸盐偶联物可能有助于激素缺乏条件下的细胞存活和适应性生长。更好地了解oops的病理生理作用可能为克服激素难治性乳腺和前列腺肿瘤提供关键信息。
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A Putative Role of Organic Anion Transporting Polypeptides (Oatps) In Cell Survival of Hormone-Dependent Breast and Prostate Cancers
Transporter proteins classified into the solute carrier (SLC) transporter superfamily are essential for import of nutrients for cell survival in organisms. In the last two decades, compelling evidence has accumulated that SLC transporters interact with clinically important anticancer agents and contribute to their pharmacokinetics, particularly the biopharmaceutical processes of absorption, elimination and distribution. Furthermore, many SLC transporters have been shown to be differentially upregulated in cancer cells, and this may represent an adaptive response to altered nutritional requirements. Thus, it is likely to utilize them as carrier for efficient drug delivery as well as pharmacological target to shut off the essential nutrients for cell growth of malignant tumors. This short review will introduce organic anion transporting polypeptides which recognize endo- and exogenous organic anionic compounds and recent findings about their upregulation in cancer cells. Besides, OATP-mediated sulfate conjugates of steroid hormone may contribute to cell survival and adapted growth under hormonedepleted conditions. Better understandings of pathophysiological role of OATPs likely provide key information to overcome hormone-refractory breast and prostate tumors.
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