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Functional expression of human organic cation transporter 3 in renal cancer cells
Author(s) -
Shnitsar Volodymyr,
Koepsell Hermann,
Burckhardt Gerhard,
Hagos Yohannes
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1198.4
Subject(s) - organic cation transport proteins , transfection , cell culture , vincristine , cancer cell , solute carrier family , cytotoxic t cell , mtt assay , transporter , cancer research , cancer , chemistry , cytotoxicity , microbiology and biotechnology , renal cell carcinoma , cell , cell growth , biology , in vitro , medicine , biochemistry , chemotherapy , oncology , gene , genetics , cyclophosphamide
Renal cancer cell (RCC) carcinoma is usually chemoresistant. This chemoresistance would be overcome when a cytostatic is applied for which the RCC possess an uptake transporter. Therefore, in the present study we investigated the expression of solute carrier (SLC) transporters in different RCC samples and their ability to interact with chemotherapeutical drugs. We tested five RCC cancer lines as well as normal and tumor tissue for expression of 30 different SLC by RT‐PCR and TaqMan real‐time PCR. In two of five RCC lines, A498 and 7860, we observed a highly significant expression of SLC22A3 (hOCT3). The uptake of organic cation [ 3 H] MPP (4‐methyl‐pyridinium iodide) into these cells and also into hOCT3 stably transfected CHO cells was highly inhibited by irinotekan and vincristine. The Ki values calculated from Dixon plots for irinotekan and vincristine are 1.72±0.45 μM and 17±4.81 μM, respectively. Cytotoxic activities of the selected drugs were tested by the MTT assay on CHO‐OCT3, A498 and ACHN cell lines. The growth of CHO‐OCT3 was inhibited by 20% more with irinotekan and by 50% more with vincristine compared to non transfected CHO cells. Similar results were obtained for A498 and ACHN cells. Thus, our data support the hypothesis that the sensitivity of tumor cells to chemotherapeutical treatment depends on the expression of transporter proteins mediating specific drug accumulation into the target cell.