(R)-(-)-1,1-(2-amino-methylpyrrorodine)-platinum(II) (DWA2114R), cis-1,1-cyclobutanedicarboxylato(2R)-2-methyl-1,4-butanediammin eplatinum(II) (NK121; CI-973) and glycolate-o,-o'-diammine platinum(II) (254-S; NSC375101D) are new platinum compounds developed in Japan. We studied the antitumor effects of these compounds on the cisplatin (cis-diamminedichloroplatinum, DDP)-resistant human leukemia cell line, K562/DDP. K562/DDP cells were 10-fold resistant to DDP, while the cells showed minimal cross-resistance to carboplatin (2.1-fold) and DWA2114R (3.3-fold), and were as sensitive to NK121 (1.6-fold) and 254-S (1.0-fold) as the parent cells. Increases in exposure time of K562 cells to DWA2114R resulted in progressive shifting of the dose-response curve to the left, or more effective cell growth inhibition of the cells. Time dependency indices (ID80 obtained from dose-response curve after 1 hr-exposure of K562 cells to drug followed by 72 hr-culture without drug/ID80 after 24 hr-exposure) of DDP, NK121 and 254-S were 10, 8 and 20, respectively. A multidrug resistant cell-line, MOLT-3/TMQ200, was as sensitive to platinum compounds as the parent MOLT-3 cells. Little or no influence of tumor cell density was observed in the growth inhibition of MOLT-3 or K562 cells induced by these new compounds even if cells were concentrated to a density of 10(8) cells/ml. These results indicate that NK121 and 254-S may overcome the drug resistance developed in the patients after treatment with DDP. The antitumor effect of DWA2114R is more dependent not only on drug-concentration but also on exposure time than that of DDP, suggesting that continuous infusion rather than bolus administration appears the favorable schedule in clinical trials.
Mendeley saves you time finding and organizing research
Choose a citation style from the tabs below