title: Organic cation transporter OCT6 mediates cisplatin uptake and resistance to cisplatin in lung cancer.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kunii
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Oguri
authors.forename: Daishi
authors.initials: D
authors.lastname: Kasai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ozasa
authors.forename: Takehiro
authors.initials: T
authors.lastname: Uemura
authors.forename: Osamu
authors.initials: O
authors.lastname: Takakuwa
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Ohkubo
authors.forename: Masaya
authors.initials: M
authors.lastname: Takemura
authors.forename: Ken
authors.initials: K
authors.lastname: Maeno
authors.forename: Akio
authors.initials: A
authors.lastname: Niimi
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D027701:Organic Cation Transport Proteins; C467737:SLC22A16 protein, human; D002945:Cisplatin