Table 1.
Response of a panel of cell lines to conventional cytotoxic drugs, tirapazamine and targeted therapeutics under normoxic (N) and hypoxic (H) conditions
| Drug | A549 | H460 | MDA MB231 | DLD1 | TK10 |
|---|---|---|---|---|---|
| 5FU (N) | 2.28 ± 0.56 | 1.97 ± 1.27 | 14.61 ± 9.23 | 3.03 ± 0.59 | 41.35 ± 7.92 |
| 5FU (H) | 15.13 ± 3.72++ | 6.54 ± 1.13++ | 39.17 ± 5.21++ | 12.62 ± 3.02++ | 72.99 ± 25.38+ |
| Dox (N) | 0.25 ± 0.04 | 0.023 ± 0.006 | 0.42 ± 0.01 | 0.074 ± 0.004 | 0.34 ± 0.03 |
| Dox (H) | 1.00 ± 0.14++ | 0.066 ± 0.011+ | 0.46 ± 0.05 | 0.43 ± 0.05++ | 0.26 ± 0.05 |
| Vinblastine (N) | 0.72 ± 0.05 | 1.23 ± 0.03 | 0.55 ± 0.06 | 2.47 ± 0.79 | 2.40 ± 0.17 |
| Vinblastine (H) | 2.13 ± 0.69++ | 1.36 ± 0.10 | 0.85 ± 0.10 | 5.28 ± 0.44+ | 7.43 ± 1.43++ |
| Tirapazamine(N) | 23.13 ± 3.41 | 22.85 ± 1.12 | 7.84 ± 0.86 | 15.91 ± 1.23 | 19.69 ± 2.54 |
| Tirapazamine(H) | 2.40 ± 1.34++ | 2.53 ± 0.92++ | 2.89 ± 0.65++ | 2.95 ± 1.68++ | 3.38 ± 1.15++ |
| Sunitinib (N) | 4.82 ± 0.31 | 3.73 ± 2.00 | 8.17 ± 1.13 | 2.85 ± 0.73 | 8.02 ± 0.63 |
| Sunitinib (H) | 4.97 ± 0.42 | 2.54 ± 0.47 | 5.08 ± 0.49 | 0.50 ± 0.09++ | 5.92 ± 0.62 |
| Sorafenib (N) | 2.74 ± 1.50 | 1.42 ± 0.13 | 0.51 ± 0.34 | 1.16 ± 0.53 | 0.25 ± 0.05 |
| Sorafenib (H) | 21.63 ± 6.12++ | 5.49 ± 0.95++ | 2.10 ± 1.38++ | 2.90 ± 0.77+ | 9.02 ± 3.05++ |
| Gefitinib (N) | 23.32 ± 3.62 | 14.90 ± 1.11 | 10.62 ± 0.82 | 10.46 ± 1.94 | 0.97 ± 0.27 |
| Gefitinib (H) | 16.69 ± 2.41 | 22.34 ± 2.12++ | 11.85 ± 0.78 | 7.22 ± 1.81+ | 9.10 ± 3.50++ |
| Masatinib (N) | 18.17 ± 0.51 | 12.47 ± 1.52 | 8.39 ± 2.02 | 16.33 ± 3.10 | 14.72 ± 3.65 |
| Masatinib (H) | 18.75 ± 2.81 | 18.47 ± 1.04++ | 12.93 ± 2.23+ | 5.34 ± 0.61++ | 10.40 ± 0.78 |
| Vandetinib (N) | 7.60 ± 3.77 | 8.75 ± 0.78 | 8.12 ± 0.99 | 6.68 ± 1.90 | 2.35 ± 1.92 |
| Vandetinib (H) | 8.07 ± 0.84 | 10.54 ± 0.37 | 5.56 ± 2.56+ | 4.25 ± 0.53+ | 1.82 ± 0.39 |
| Dasatinib (N) | 0.17 ± 0.01 | 14.52 ± 1.48 | 33.0 ± 9.53* | 2.25 ± 0.04 | 3.62 ± 1.08* |
| Dasatinib (H) | 23.92 ± 8.58++ | 11.18 ± 1.27 | 6.0 ± 4.35*++ | 25.09 ± 4.43++ | 12.17 ± 2.55*++ |
| Nilotinib (N) | 7.61 ± 0.86 | 5.86 ± 1.89 | 2.81 ± 1.00 | 8.08 ± 2.64 | 1.12 ± 0.68 |
| Nilotinib (H) | 9.98 ± 1.66 | 9.04 ± 0.94+ | 1.73 ± 1.02 | 5.39 ± 0.42 | 24.53 ± 0.99++ |
| Imatinib (N) | 32.77 ± 0.85 | 23.76 ± 2.15 | 18.28 ± 0.68 | 21.58 ± 1.68 | 15.90 ± 3.17 |
| Imatinib (H) | 33.28 ± 3.85 | 22.89 ± 3.10 | 19.69 ± 1.30 | 17.54 ± 1.20 | 18.96 ± 1.71 |
| Erlotinib (N) | 3.74 ± 0.67 | 11.58 ± 0.85 | 15.70 ± 0.36 | 10.33 ± 0.65 | 4.71 ± 2.12 |
| Erlotinib (H) | 33.83 ± 3.23++ | 29.58 ± 10.99++ | 20.11 ± 0.54+ | 7.56 ± 0.81+ | 47.25 ± 8.41++ |
Cells were pre-incubated under normoxic and hypoxic (0.1% oxygen) conditions for 24 h before a 96 h exposure to each drug. Cell survival was determined using the MTT assay and results are expressed as IC50 values. The units are μM in all cases with the exception of those marked by an asterisk where the units are in nM. Each value represents the mean ± SD of three independent experiments. Statistical analysis comparing response under hypoxia to aerobic conditions was performed using Student's t-test and P-values of <0.05 and 0.01 are represented as + and ++ respectively.