title: Establishment and gene analysis of a cisplatin-resistant cell line, Sa-3R, derived from oral squamous cell carcinoma.
abstract: Cisplatin (CDDP) is widely used for chemotherapy of many malignancies, especially of oral squamous cell carcinoma (SCC). However, because the mechanism of resistance to CDDP is unclear, we established a CDDP-resistant cell line, Sa-3R, from a CDDP-sensitive cell line, Sa-3, which was derived from moderately differentiated SCC of the lower gingiva. The 3-(3,4-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide assay indicated that Sa-3R has 7.5-fold greater resistance to CDDP than Sa-3. Comparing gene expression levels in the cell lines using an in-house cDNA microarray, which represented 2,201 oral disease origin genes, many differentially expressed genes were identified. The ATP-binding cassette transporter genes (MDR-1, MRP-1, and MRP-2), and FANCONI, GRP58, FLJ12089, and SPINT-2 were up-regulated, whereas FOSL1, MRPS27, and PGK-1 were down-regulated. These results were confirmed by semiquantitative reverse transcriptase-polymerase chain reaction. The Sa-3/Sa-3R cell lines could be useful to identify the candidates responsible for the mechanism of CDDP-resistance and the up- or down-regulated genes identified by the gene expression profiles in the Sa-3R cell line may be, in part, associated with the mechanism.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Medicine, Wakayama Medical University, Kimiidera 811-1, Wakayama 641-8509, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Nakatani
authors.forename: Megumi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Uzawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Wada
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanzawa
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Fujita
mesh_terms: D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D004396:Coloring Agents / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology*; D000089762:Multidrug Resistance-Associated Protein 2; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C000715087:ABCC2 protein, human; D004396:Coloring Agents; D018076:DNA, Complementary; D000089762:Multidrug Resistance-Associated Protein 2; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D002945:Cisplatin