Zs. Chen et al., AN ACTIVE EFFLUX SYSTEM FOR HEAVY-METALS IN CISPLATIN-RESISTANT HUMANKB CARCINOMA-CELLS, Experimental cell research, 240(2), 1998, pp. 312-320
The mechanism for cisplatin resistance in cisplatin-resistant KCP-4 ce
lls was studied. Although multidrug resistance-associated protein (MRP
) was not detected in KCP-4 cells, the cells were more resistant to he
avy metals than multidrug-resistant C-A120 cells that overexpressed MR
P, KCP-4 cells expressed metallothionein, but it was scarcely involved
in cisplatin resistance in these cells. KCP-4 cells did not express c
analicular multispecific organic anion transporter (cMOAT), The glutat
hione(GSH) level was 4.7-fold higher in KCP-4 cells than in KB-3-1 cel
ls. When the GSH level in KCP-4 cells was decreased by treating the ce
lls with buthionine sulfoximine and nitrofurantoin, the accumulation o
f and sensitivity to cispaltin in the cells were increased. C-A120 cel
ls were only 3.0-fold more resistant to cisplatin than KB-3-1 cells an
d this resistance was not affected by the increased glutathione level.
The accumulation of platinum in C-A120 and KCP-4 cells was 68.5 and 2
0.4% of that in KB-3-1 cells, respectively, while the intracellular le
vels of antimony potassium tartrate in C-A120 and KCP-4 cells were 13.
2 and 9.9% of that in KB-3-1 cells, respectively. The ATP-dependent ef
flux of antimony was enhanced in both C-A120 and KCP-4 cells. These re
sults, taken together, suggest an efflux pump for heavy metals differe
nt from MRP and cMOAT is involved in cisplatin resistance in KCP-4 cel
ls. (C) 1998 Academic Press.