Table 1.

Cytotoxicity profile of MAC-321 in a panel of PTX-sensitive and -resistant tumor cell linesa

Cell LineTumor OriginP-glycoprotein ExpressionbIC50 (nm)
MAC-321PTXDTXVinblastine
A549NSCLC01.2 ± 0.77.5 ± 1.81.9 ± 0.73.7 ± 0.9
HCT-116colon03.1 ± 0.78.2 ± 1.45.4 ± 0.82.3 ± 1.5
NCI-H838NSCLC03.3 ± 0.32.1 ± 0.96.3 ± 0.70.9 ± 0.6
KB-3-1epidermoid01.3 ± 0.53.9 ± 1.31.1 ± 0.60.8 ± 0.4
1A9 (A2780 subclone)ovarian01.7 ± 0.65.1 ± 0.91.9 ± 1.01.9 ± 0.2
Average ± SD2.1 ± 1.005.4 ± 2.503.3 ± 2.401.9 ± 1.20
MX-1Wbreast+2.6 ± 1.415.4 ± 2.95.78 ± 2.37n.d.
NCI-H1299NSCLC++5.3 ± 1.837.7 ± 2.312.9 ± 0.986.33 ± 1.24
DLD-1colon+++1.2 ± 0.932.5 ± 2.414.29 ± 1.1815.38 ± 0.62
HCT-15colon++++3.3 ± 0.2438.6 ± 1.954.62 ± 0.1915.81 ± 1.97
Average ± SD3.1 ± 1.70131.0 ± 205.3021.9 ± 22.109.4 ± 7.75
COLO 205colonn.d.0.6 ± 0.17.0 ± 2.30.6 ± 0.21.3 ± 1.0
LOXmelanoman.d.4.3 ± 2.417.4 ± 1.46.9 ± 0.62.8 ± 1.7
Panc-1pancreaticn.d.1.2 ± 0.96.2 ± 1.71.9 ± 1.2n.d.
AsPc-1pancreaticn.d.1.2 ± 0.32.4 ± 0.31.9 ± 0.7n.d.
Capan-1pancreaticn.d.1.2 ± 1.02.6 ± 0.81.5 ± 0.9n.d.
Average ± SD2.7 ± 1.507.1 ± 6.102.6 ± 2.500.8 ± 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.