Establishment and characterization of a cisplatin-resistant human neuroblastoma cell line

Background: To investigate the mechanisms of cisplatin (CDDP)-resistance in neuroblastoma(NB), we established a CDDP-resistant human NB cell line, BM1 R2. Materials and Methods: We characterized BM1R2 in terms of the susceptib ilities to other anticancer agents, MDR1 and MRP expression, MYCN amplifica tion, intracellular gultathione-S-transrerase (GST-pi), metallothionein(MT) and gultathione(GSH) levels, and immunocytochemical and cytogenetic featur es. Results: When compared to parent BM1 line, BM1R2 exhibited a 17.0-fold resistance to CDDP and cross-resistance to other agents. MRP expression was only observed in BM1R2, whereas MDR1 was expressed in both lines. Notably higher intracellular GST-pi and MT levels were observed in BM1R2 cells. MYC N amplifications were 50 and 6 copies in BM1 and BM1R2, respectively, and a dditional aberrations were observed in chromosome 1 and 2 in BM1R2. Conclus ion: It was suggested that GST-pi and MT could exert crucial roles on CDDP- resistance in our system. BM1R2 is of great interest for investigating the mechanisms of CDDP-resistance in NB.