Cytotoxicity profile of MAC-321 in a panel of PTX-sensitive and -resistant tumor cell linesa
Cell Line | Tumor Origin | P-glycoprotein Expressionb | IC50 (nm) | ||||||
---|---|---|---|---|---|---|---|---|---|
MAC-321 | PTX | DTX | Vinblastine | ||||||
A549 | NSCLC | 0 | 1.2 ± 0.7 | 7.5 ± 1.8 | 1.9 ± 0.7 | 3.7 ± 0.9 | |||
HCT-116 | colon | 0 | 3.1 ± 0.7 | 8.2 ± 1.4 | 5.4 ± 0.8 | 2.3 ± 1.5 | |||
NCI-H838 | NSCLC | 0 | 3.3 ± 0.3 | 2.1 ± 0.9 | 6.3 ± 0.7 | 0.9 ± 0.6 | |||
KB-3-1 | epidermoid | 0 | 1.3 ± 0.5 | 3.9 ± 1.3 | 1.1 ± 0.6 | 0.8 ± 0.4 | |||
1A9 (A2780 subclone) | ovarian | 0 | 1.7 ± 0.6 | 5.1 ± 0.9 | 1.9 ± 1.0 | 1.9 ± 0.2 | |||
Average ± SD | 2.1 ± 1.00 | 5.4 ± 2.50 | 3.3 ± 2.40 | 1.9 ± 1.20 | |||||
MX-1W | breast | + | 2.6 ± 1.4 | 15.4 ± 2.9 | 5.78 ± 2.37 | n.d. | |||
NCI-H1299 | NSCLC | ++ | 5.3 ± 1.8 | 37.7 ± 2.3 | 12.9 ± 0.98 | 6.33 ± 1.24 | |||
DLD-1 | colon | +++ | 1.2 ± 0.9 | 32.5 ± 2.4 | 14.29 ± 1.18 | 15.38 ± 0.62 | |||
HCT-15 | colon | ++++ | 3.3 ± 0.2 | 438.6 ± 1.9 | 54.62 ± 0.19 | 15.81 ± 1.97 | |||
Average ± SD | 3.1 ± 1.70 | 131.0 ± 205.30 | 21.9 ± 22.10 | 9.4 ± 7.75 | |||||
COLO 205 | colon | n.d. | 0.6 ± 0.1 | 7.0 ± 2.3 | 0.6 ± 0.2 | 1.3 ± 1.0 | |||
LOX | melanoma | n.d. | 4.3 ± 2.4 | 17.4 ± 1.4 | 6.9 ± 0.6 | 2.8 ± 1.7 | |||
Panc-1 | pancreatic | n.d. | 1.2 ± 0.9 | 6.2 ± 1.7 | 1.9 ± 1.2 | n.d. | |||
AsPc-1 | pancreatic | n.d. | 1.2 ± 0.3 | 2.4 ± 0.3 | 1.9 ± 0.7 | n.d. | |||
Capan-1 | pancreatic | n.d. | 1.2 ± 1.0 | 2.6 ± 0.8 | 1.5 ± 0.9 | n.d. | |||
Average ± SD | 2.7 ± 1.50 | 7.1 ± 6.10 | 2.6 ± 2.50 | 0.8 ± 1.20 |
↵a Cell toxicity was measured using the SRB protein stain as an assessment of protein content and survival after a 72-h incubation period with MAC-321, PTX, DTX, or vinblastine as described in “Materials and Methods.” IC50 ± SD values are representative of three independent experiments.
↵b P-glycoprotein expression was determined by Western blotting and quantitative real-time RT-PCR using MDR-specific antibodies and probes, respectively, as described in “Materials and Methods.” Scoring code based on Western blotting: 0, not detected; + to ++++, low to high expression; n.d., not determined.