Cytotoxicity profile of MAC-321 versus standard chemotherapeutics in PTX- and Epo-resistant cell lines that contain mutations in the taxane-binding site of β-tubulina
Compound | IC50 (nm)* | Relative Resistanceb | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1A9 | 1A9 PTX10 | 1A9 PTX22 | 1A9 EpoA8 | 1A9 PTX10 | 1A9 PTX22 | EpoA8 | ||||||||
MAC -321 | 1.6 ± 0.6 | 5.4 ± 2.7 | 8 ± 1.4 | 2.6 ± 1.6 | 3.4 | 5.0 | 1.6 | |||||||
PTX | 5.1 ± 1.0 | 26.6 ± 16.3 | 89.2 ± 55.6 | 20.9 ± 10.8 | 5.2 | 17.5 | 4.1 | |||||||
DTX | 1.8 ± 0.6 | 7.5 ± 0.3 | 7.9 ± 0.2 | 2.2 ± 1.2 | 4.2 | 4.4 | 1.2 | |||||||
EpoA | 1.8 ± 0.5 | 16.0 ± 49.0 | 4.1 ± 3.3 | 31.8 ± 14.0 | 8.9 | 2.3 | 17.7 | |||||||
Compound | IC50 (nm)** | Relative Resistanceb | ||||||||||||
A549 | A549.EpoB40 | A549.EpoB40 | ||||||||||||
MAC-321 | 1.1 ± 0.6 | 11.3 ± 1.2 | 10.7 | |||||||||||
PTX | 7.5 ± 1.3 | 156.9 ± 16.9 | 20.8 | |||||||||||
DTX | 1.9 ± 0.7 | 31.8 ± 1.6 | 16.6 | |||||||||||
EpoB | 1.0 ± 0.1 | 91.5 ± 3.9 | 95.3 |
↵a Parental cells and their resistant cell counterpart were grown in the presence of the indicated agents for 3 days and growth assessed by SRB staining (*) or ATP-binding (**) as described in “Materials and Methods.” Data are reported as average IC50 ± SD.
↵b Average relative resistance is defined as the ratio of the IC50 of the resistant cell model to that of the respective sensitive/parental cell counterpart.