title: Cross-resistance of platinum derivatives in H-1R, a cisplatin-resistant cell line.
abstract: We previously established H-1R cells, a cisplatin (CDDP)-resistant cell line, from H-1 cells, a CDDP-sensitive oral carcinoma cell line. The aim of this study was to identify the molecular mechanism of cross-resistance to antitumor drugs containing a platinum agent in H-1R cells. The 3-(3,4-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay and clonogenecity assay indicated that H-1R cells showed strong cross-resistance to carboplatin, nedaplatin and oxaliplatin. The expression status of the copper transporter and organic cation transporters was confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction. The transporters ATP7A, ATP7B, hCtr1, hOCT1 and hOCT2 were up-regulated, whereas hOCT3 was down-regulated. The cellular glutathione level was elevated 2-fold in H-1R cells compared with H-1 cells. Our results suggested that H-1 and H-1R cells may be useful in searching for candidate genes responsible for cross-resistance to platinum derivatives and for further studies to understand the mechanism of platinum resistance.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Wakayama Medical University, Wakayama 641-8509, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Negoro
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yamano
authors.forename: Dai
authors.initials: D
authors.lastname: Nakashima
authors.forename: Kengo
authors.initials: K
authors.lastname: Saito
authors.forename: Ken
authors.initials: K
authors.lastname: Nakatani
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiiba
authors.forename: Hiroki
authors.initials: H
authors.lastname: Bukawa
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yokoe
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Uzawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Wada
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanzawa
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Fujita
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology; D027682:Cation Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004354:Drug Screening Assays, Antitumor; D015870:Gene Expression; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D027682:Cation Transport Proteins; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; D000077150:Oxaliplatin; C053989:nedaplatin; D016190:Carboplatin; D002945:Cisplatin