Cross-resistance of platinum derivatives in H-1R, a cisplatin-resistant cell line.
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.
Negoro
Kenji
K
Department of Oral and Maxillofacial Surgery, Wakayama Medical University, Wakayama 641-8509, Japan.
Yamano
Yukio
Y
Nakashima
Dai
D
Saito
Kengo
K
Nakatani
Ken
K
Shiiba
Masashi
M
Bukawa
Hiroki
H
Yokoe
Hidetaka
H
Uzawa
Katsuhiro
K
Wada
Takeshi
T
Tanzawa
Hideki
H
Fujita
Shigeyuki
S
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
D000970:Antineoplastic Agents; D027682:Cation Transport Proteins; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; D000077150:Oxaliplatin; C053989:nedaplatin; D016190:Carboplatin; D002945:Cisplatin