Table 2. ABC-transporter proteins are not involved in C6-SM-enhanced doxorubicin uptake.
| Cell type | C6-SM 10 μM | ATP depletion | PSC833 5 μM | MK571 12.5 μM | Mrp1−/− Mdr1a−/− Mdr1b/− | Doxorubicin (% of control±s.d.) |
|---|---|---|---|---|---|---|
| BAEC | − | − | − | − | − | 100.0±28.5 |
| + | − | − | − | − | 369.0±113.0 | |
| − | + | − | − | − | 108.2±46.7 | |
| + | + | − | − | − | 410.9±157.0 | |
| − | − | + | − | − | 76.0±15.6 | |
| + | − | + | − | − | 278.1±40.7 | |
| − | − | − | + | − | 103.5±30.2 | |
| + | − | − | + | − | 323.3±23.0 | |
| Kidney fibroblasts | − | − | − | − | − | 100.0±4.4 |
| + | − | − | − | − | 331.8±50.2 | |
| − | − | − | − | + | 101.7±14.3 | |
| + | − | − | − | + | 385.1±24.7 |
Doxorubicin accumulation was monitored in the indicated cell types during 60 min, in the absence or presence of 10 μM C6-SM. Cells were ATP-depleted during a 90 min preincubation in glucose-free culture medium, supplemented with 10 mM 2-deoxy-D-glucose and 10 mM sodium azide. Alternatively, 5 μM PSC833 or 12.5 μM MK571 was administered to the cells at least 15 min before exposure to doxorubicin. Kidney fibroblasts were isolated from control mice or from Mrp1/Mdr1a/Mdr1b triple knockout mice. All data are expressed as mean percentages±s.d. (n=3) to the untreated controls of either BAEC or fibroblasts.