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01.05.2015 | Original Article

Organic cation transporter OCT6 mediates cisplatin uptake and resistance to cisplatin in lung cancer

verfasst von: Eiji Kunii, Tetsuya Oguri, Daishi Kasai, Hiroaki Ozasa, Takehiro Uemura, Osamu Takakuwa, Hirotsugu Ohkubo, Masaya Takemura, Ken Maeno, Akio Niimi

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2015

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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.

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Titel: Organic cation transporter OCT6 mediates cisplatin uptake and resistance to cisplatin in lung cancer
verfasst von: Eiji Kunii
Tetsuya Oguri
Daishi Kasai
Hiroaki Ozasa
Takehiro Uemura
Osamu Takakuwa
Hirotsugu Ohkubo
Masaya Takemura
Ken Maeno
Akio Niimi
Publikationsdatum: 01.05.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 5/2015
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-015-2723-x

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Organic cation transporter OCT6 mediates cisplatin uptake and resistance to cisplatin in lung cancer