title: Establishment and characterization of a cisplatin-resistant cell line, KB-R, derived from oral carcinoma cell line, KB.
abstract: To investigate the mechanism of the resistance to cisplatin (CDDP), we established the CDDP-resistant cell line, KB-R, from CDDP-sensitive oral carcinoma cell line, KB. The 3-(3, 4-dimethyl-thiazol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) assay indicated that KB-R is 5.5-fold more resistant to CDDP than KB. Microarray analysis indicated that the expression levels of 1,718 genes were elevated at least five-fold or more in KB-R, compared with KB. The expression status of ATP binding cassette (ABC) transporter genes, which belong to multi-drug resistance genes, was confirmed by semiquantitative reverse transcriptase-polymerase chain reaction and real-time PCR. MRP1 and MRP2 were up-regulated, whereas MDR1 was down-regulated. Pathway and ontology analysis using the Ingenuity Pathway Analysis tool indicated three highly significant genetic networks including 105 of the 1,718 overexpressed genes and one network including 35 'cell-to-cell signaling and interaction' related genes. Our results suggested that these cell lines, KB and KB-R, may be useful for searching the candidate genes responsible for CDDP-resistance and for further study to understand the mechanism of CDDP-resistance.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Medicine, Wakayama Medical University, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Negoro
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yamano
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Fushimi
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: Hidetaka
authors.initials: H
authors.lastname: Yokoe
authors.forename: Hiroki
authors.initials: H
authors.lastname: Bukawa
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*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D019450:Genes, MDR; D006801:Humans; D007624:KB Cells; D009062:Mouth Neoplasms / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin