In vitro establishment of cis-diammine-dichloroplatinum(II) resistant lungcancer cell line and modulation of apoptotic gene expression as a mechanism of resistant phenotype

After exposure of H460 cells to an increasing concentrations of cis-diammin e-dichloroplatinum(II) (cisplatin, CDDP) for 6 months, cisplatin resistant cells were isolated (H460/CIS). The biologic behaviors of H460 and H460/CIS cells were tested using animal experiments. Only the resistant cells devel oped lung metastases despite cisplatin treatment. The characteristics of H4 60/CIS cells are as follows, MTT analyses revealed that H460/CIS cells were markedly resistant to cisplatin compared with their parental cells. Also, H460/CIS cells exhibited cross-resistance to DNA damaging agents such as do xorubicin (DXR) and etoposide. Cisplatin treatment dramatically increased p 53 expression in parental cells but not in H460/CIS cells which expressed b asal levels of p53. Without cisplatin treatment, Bcl-2 and Bax were express ed in H460/CIS cells, but not in parental cell. Our data suggested that p53 , Bax and Bcl-2 were up-regulated in H460/CIS cells. These changes could ex plain some of the mechanisms of cisplatin resistance. Thus, H460/CIS could be useful to investigate the mechanisms of drug resistance to cisplatin inc luding apoptotic gene expressions conferring drug resistance, thereby makin g progress in the treatment of cisplatin-resistant tumor cells. (C) 2001 El sevier Science Ireland Ltd. All rights reserved.