Abstract
We have attempted the overcoming of anticancer drug resistance in murine leukemia by unsaturated aliphatic compouns and investigated the drug up-take into cells using adriamycin(ADM)resistant mouse P 388 leukemia(P 388/ADM). When 150 μM unsaturated fatty acids such as oleic acid(OA, C18 : 1 Δ9), linoleic acid(LA, C18 : 2 Δ9-12)and α-linolenic acid(α-LNA, C18 : 3 Δ9-12-15)were added along with ADM to the P 388/ADM or ADM sensitive P 388 (P 388/S)culture in vitro, ADM resistance was greatly reduced, and especially α-LNA completely overcomed the resistance. In addi-tion, α-LNA showed a stronger its own killing activity to P 388/ADM than OA and LA. These fatty acids also potentiated the cytotoxicity of ADM against P 388/S. The uptake of ADM was increased by these fatty acids, however, large dif-ferences of enhancing rate at 3h were observed between P 388/S(2-7 fold)and P 388/ADM(16-30 fold). These findings suggest that unsaturated fatty acids can overcome ADM resistance in P 388 leuke-mia by enhancing the drug uptake and its own cell killing activity.
