Expression of Human Organic Cation Transporter 3 in Kidney Carcinoma Cell Lines Increases Chemosensitivity to Melphalan, Irinotecan, and Vincristine

摘要: Renal cell carcinoma (RCC) is usually chemoresistant. This chemoresistance could be overcome if specific cytostatics are applied for which the RCC expresses an uptake transporter. In present study, we investigated expression of solute carrier (SLC) transporters in different lines and their ability to interact with chemotherapeutics. We tested five SLCs by reverse transcription-PCR TaqMan real-time PCR. two lines, A498 7860, observed a highly significant SLC22A3 (hOCT3). Uptake organic cation [(3)H]MPP (4-methyl-pyridinium iodide) into these cells also hOCT3 stably transfected Chinese hamster ovary (CHO) was inhibited irinotecan, vincristine, melphalan. The K(i) values [determined from Dixon plots] melphalan were 1.72 +/- 0.45 micromol/L, 17 4.81 366 51 respectively. Cytotoxic activities selected drugs [(3)H]thymidine incorporation 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays on CHO-hOCT3, (high hOCT3), ACHN (low hOCT3). growth CHO-hOCT3 20% more irinotecan 50% vincristine compared nontransfected CHO cells. Melphalan produced 30% inhibition hOCT3-expressing nonexpressing control Similar results obtained Thus, our data support hypothesis that sensitivity tumor chemotherapeutic treatment depends transporter proteins mediating drug accumulation target