EFFECTS OF NEW PLATINUM ANTICANCER DRUGS IN HUMAN CIS-DIAMMINEDICHLOROPLATINUM(II) SENSITIVE AND RESISTANT OVARIAN-CARCINOMA CELLS

The cytotoxicity of cis-diamminedichloroplatinum (II) (CDDP) and 4 analogues was examined in CDDP-sensitive and resistant cell lines derived from a patient with serous cystadenocarcinoma of the ovary. Resistant cells had 7.4-fold resistance to CDDP compared with sensitive cells and were cross-resistant to CDDP analogues. The resistance factors (RF) were for the 4 analogues, 254S, CBDCA, NK121, and DWA2114R (DWA), 4.3, 3.0, 2.3, and 1.6. In both cell lines, intracellular CDDP levels increased linearly with exposure time to CDDP and the levels decreased a little 2 hrs after the medium was exchanged for CDDP-free medium. In resistant cells, the level of CDDP decreased to 20.2% of that in sensitive cells. These results suggested that the influx was more important than the efflux in CDDP-resistance. The intracellular platinum level for the 4 CDDP analogues was also lower in resistant cells than in sensitive cells. The percentage platinum level in resistant cells compared to sensitive cells was inversely correlated with the RF. These results suggested that resistance to CDDP and other platinum drugs was due, in part, to reduced intracellular drug levels. DWA was the most effective CDDP analogue in resistant cells.