Human Organic Cation Transporter 1 Is Expressed in Lymphoma Cells and Increases Susceptibility to Irinotecan and Paclitaxel

被引:39
作者
Gupta, Shivangi [1 ]
Wulf, Gerald [2 ]
Henjakovic, Maja [1 ]
Koepsell, Hermann [3 ]
Burckhardt, Gerhard [1 ]
Hagos, Yohannes [1 ]
机构
[1] Univ Med Gottingen, Abt Vegetat Physiol & Pathophysiol, Gottingen, Germany
[2] Univ Med Gottingen, Abt Hamatol & Onkol, Gottingen, Germany
[3] Univ Wurzburg, Lehrstuhl Anat 1, Wurzburg, Germany
关键词
REDUCED FOLATE CARRIER; ANTIEPILEPTIC DRUGS REDUCE; METHOTREXATE CHEMOTHERAPY; CANCER; PHARMACOKINETICS; POLYMORPHISMS; CYTOTOXICITY; EFFICACY; THERAPY;
D O I
10.1124/jpet.111.190561
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Antineoplastic agents directed at nuclear and cytoplasmic targets in tumor cells represent the current mainstay of treatment for patients with disseminated malignant diseases. Cellular uptake of antineoplastics is a prerequisite for their efficacy. Five of six lymphoma cell lines as well as primary samples from chronic lymphocytic leukemia patients demonstrated significant expression of SLC22A1 mRNA coding for organic cation transporter 1 (OCT1). Functionally, the antineoplastic agents irinotecan, mitoxantrone, and paclitaxel inhibited the uptake of the organic cation [H-3] 1-methyl-4-pyridinium iodide into OCT1-transfected Chinese hamster ovary model cells, with K-i values of 1.7, 85, and 50 mu M, respectively. Correspondingly, OCT1-positive cell lines and transfectants exhibited significantly higher susceptibilities to the cytotoxic effects of irinotecan and paclitaxel compared with those of OCT1-negative controls. We hypothesize that OCT1 can contribute to the susceptibility of cancer cells to selected antineoplastic drugs. In the future, an expression analysis of the transporters and the application of transporter-specific antineoplastic agents could help to tailor cancer therapy.
引用
收藏
页码:16 / 23
页数:8
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