Characterization of the organic cation transporter SLC22A16: A doxorubicin importer
Characterization of the organic cation transporter SLC22A16: A doxorubicin importer
复制标题
DOI：
10.1016/j.bbrc.2005.05.174
复制
发表时间：
2005-08-05
影响因子：
3.1
通讯作者：
Abe, T
中科院分区：
文献类型：
--
作者：
Okabe, M;Unno, M;Abe, T
特定的外排转运蛋白，例如 P-糖蛋白，已被证明可以通过减少抗癌药物的细胞内积累来赋予耐药性。了解流入转运蛋白和流出转运蛋白对于克服这种阻力至关重要。我们报告了有机阳离子转运蛋白 SLC22A16 的表达谱和药理学特征。我们的实验结果表明，SLC22A16 是癌细胞中阿霉素摄取的介质。实时定量 RT-PCR 分析表明，SLC22A16 在急性白血病患者的原始样本中表达。注射SLC22A16 cRNA的非洲爪蟾卵母细胞以可饱和且剂量依赖性的方式导入阿霉素（一种广泛用于治疗血液恶性肿瘤的抗癌药物）。阿霉素输入的表观 K-m 值为 5.2 +/- 0.4 μM。在细胞毒性测定中，过表达 SLC22A16 细胞的白血病 Jurkat 细胞的稳定转染子对阿霉素 (2 μM) 处理变得显着更敏感。 SLC22A16 的表征将有助于设计针对血液恶性肿瘤的新疗法。 (c) 2005 Elsevier Inc. 保留所有权利。
Specific efflux transporters, such as P-glycoprotein, have been shown to confer drug resistance by decreasing the intracellular accumulation of anticancer drugs. Understanding influx transporters, as well as efflux transporters, is essential to overcome this resistance. We report the expression profile and pharmacological characterization of an organic cation transporter, SLC22A16. The results of our experiments indicate that SLC22A16 is a mediator of doxorubicin uptake in cancer cells. Quantitative real-time RT-PCR analyses show that SLC22A16 is expressed in primary samples taken from patients with acute leukemia. Xenopus oocytes injected with SLC22A16 cRNA import doxorubicin, a widely used anticancer drug for hematological malignancies, in a saturable and dose-dependent manner. The apparent K-m value for doxorubicin import was 5.2 +/- 0.4 mu M. In cytotoxic assays, stable transfectants of leukemic Jurkat cells overexpressing SLC22A16 cells became significantly more sensitive to doxorubicin (2 mu M) treatment. Characterization of SLC22A16 will help in designing novel therapies targeting hematological malignancies. (c) 2005 Elsevier Inc. All rights reserved.