[Establishment of human ovarian cancer cisplatin resistant cell line COC1/DDP and its mechanism of resistance].

OBJECTIVE: To establish cisplatin (DDP)-resistant subline of human ovarian cancer and investigate the mechanism responsible for resistance to DDP. METHODS: A DDP-resistant human ovarian adenocarcinoma cell subline (COC1/DDP) was developed by contineous stepwise selection in increasing concentration of DDP from the parent cell line COC1 in vitro. The multiple changes of biological properties in COC1/DDP cell line were determined. RESULTS: COC1/DDP cells were of 6.5-fold resistance to DDP and displayed significant cross-resistant with carplatin and mitomycin C, but still remained sensitive to 5-fluorouracil and adriamycin. As compared to the parent cells, in COC1/DDP cells: the doubling time was reduced by 12.9%. Cellular content of DDP was diminished by more one half and the DNA-interstrand cross-links (ISC) was lower than that of the sensitive cells. Evidence of P-glycoprotein overexpression was not shown in COC1 and COC1/DDP cell lines by means of immunohistochemical method. CONCLUSIONS: The primary factor causing COC1/DDP resistance to DDP is the reduction of intracellular platinum accumulation and DNA ISC formation. The resistance is not considered to be associated with the multidrug resistant and P-glycoprotein.