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- Title
Organic cation transporter OCT6 mediates cisplatin uptake and resistance to cisplatin in lung cancer.
- Authors
Kunii, Eiji; Oguri, Tetsuya; Kasai, Daishi; Ozasa, Hiroaki; Uemura, Takehiro; Takakuwa, Osamu; Ohkubo, Hirotsugu; Takemura, Masaya; Maeno, Ken; Niimi, Akio
- Abstract
Purpose: The purposes of this study were to determine whether organic cation transporters (OCTs) can mediate platinum uptake, and whether OCT down-regulation confers resistance against cisplatin (CDDP) in cancer cells. Methods: Two lung cancer cell lines, PC-6 and PC-14, and their CDDP-resistant derivatives, PC-6/CDDP and PC-14/CDDP, were analyzed. OCT expression levels were assayed using quantitative RT-PCR and Western blotting. Additionally, the effect of OCT6 overexpression, induced by transfection of the OCT6 gene SLC22A16 using a forced expression vector, on cellular sensitivity to CDDP and on intracellular platinum accumulation was measured using PC-14/CDDP cells. Results: Both gene and protein expression of OCT6 were decreased in both CDDP-resistant cell lines compared with their expression in their respective parental cells. Intracellular accumulation of platinum was decreased in PC-14/CDDP cells compared with the parental cells after CDDP treatment. Furthermore, OCT6 overexpression induced by transfection of the OCT6 gene ( SLC22A16) forced expression vector-sensitized PC-14/CDDP cells to CDDP and oxaliplatin (L-OHP) concomitant with increased intracellular concentration of platinum. Conclusion: OCT6 is a mediator of platinum uptake in cancer cells, and down-regulation of OCT6 is possibly one of the mechanisms of resistance against cisplatin in lung cancer.
- Subjects
CISPLATIN; ORGANIC cation transporters; LUNG cancer; DRUG resistance in cancer cells; CELL lines; GENE expression
- Publication
Cancer Chemotherapy & Pharmacology, 2015, Vol 75, Issue 5, p985
- ISSN
0344-5704
- Publication type
Article
- DOI
10.1007/s00280-015-2723-x