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Oncol Rep. 2005 Apr;13(4):709-14.

Establishment and gene analysis of a cisplatin-resistant cell line, Sa-3R, derived from oral squamous cell carcinoma.

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Department of Oral and Maxillofacial Surgery, School of Medicine, Wakayama Medical University, Kimiidera 811-1, Wakayama 641-8509, Japan.


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.

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