Research Article
Rapid Screening of Novel Agents for Combination Therapy in Sarcomas
Table 2
Cell viability IC50 values and drug interaction measurements.
(a) Cell viability |
| Sarcoma type/cell line | Vorinostat | Etoposide | Sorafenib | Topotecan | Dasatinib | MK-2206 | Triciribine | IC50 (µM) | SEM | n | IC50 (µM) | SEM | n | IC50 (µM) | SEM | n | IC50 (nM) | SEM | n | IC50 (µM) | SEM | n | IC50 (µM) | SEM | n | IC50 (µM) | SEM | n |
| Ewing | | | | | | | | | | | | | | | | | | | | | | A-673 | 1.5 | 0.46 | 3 | 2.5 | 0.92 | 6 | | | | 16 | 4.9 | 5 | 6.2 | 1.7 | 11 | | | | 15 | 7.6 | 8 | RD-ES | 0.52 | | 1 | 1.5 | 0.55 | 22 | 6.5 | 1.7 | 2 | 6.8 | 1.7 | 15 | 12 | 2.4 | 13 | 7.3 | 0.62 | 28 | 6.3 | 2.8 | 26 | SK-ES-1 | 1.1 | 0.17 | 8 | 0.47 | 0.071 | 21 | 6.9 | 1.0 | 4 | 42 | 15 | 22 | 11 | 1.5 | 19 | 4.3 | 0.41 | 41 | 15 | 4.2 | 11 | Osteosarcoma | | | | | | | | | | | | | | | | | | | | | | MNNG HOS | 4.3 | 1.2 | 4 | 5.6 | 2.0 | 15 | 8.0 | 0.71 | 3 | 310 | 140 | 20 | 5.8 | 0.77 | 22 | 9.2 | 0.55 | 40 | 69 | 27 | 3 | U2-0S | 1.6 | 0.25 | 8 | 6.8 | 1.1 | 14 | 4.9 | 0.75 | 2 | 190 | 56 | 7 | 6.4 | 0.76 | 19 | 11 | 0.72 | 29 | 19 | 5.0 | 11 | Rhabdomyosarcoma | | | | | | | | | | | | | | | | | | | | | | A-204 | 2.2 | 0.38 | 8 | 3.5 | 1.0 | 22 | 2.6 | 1.7 | 3 | 64 | 9.4 | 26 | 4.2 | 1.2 | 13 | 7.0 | 0.91 | 30 | 18 | 5.0 | 13 | Fibrosarcoma | | | | | | | | | | | | | | | | | | | | | | HT-1080 | 2.8 | 0.23 | 8 | 7.4 | 2.0 | 24 | | | | 400 | 200 | 14 | 8.6 | 0.96 | 23 | 11 | 0.58 | 30 | 14 | 2.5 | 13 | Leiomyosarcoma | | | | | | | | | | | | | | | | | | | | | | SK-LMS-1 | 2.9 | 0.45 | 6 | 4.8 | 1.1 | 14 | | | | 80 | 15 | 21 | 7.8 | 0.99 | 19 | 7.7 | 0.60 | 30 | 8.0 | 1.7 | 26 | SK-UT-1 | 3.4 | 0.51 | 7 | 2.5 | 1.2 | 22 | | | | 350 | 220 | 21 | 9.9 | 1.1 | 20 | 6.9 | 0.56 | 42 | 30 | 19 | 3 | Liposarcoma | | | | | | | | | | | | | | | | | | | | | | SW-872 | 2.5 | 0.41 | 7 | 2.9 | 0.84 | 21 | | | | 73 | 27 | 21 | 4.6 | 0.72 | 23 | 7.9 | 0.57 | 41 | 18 | 3.6 | 7 |
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(b) Drug interaction measurements |
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Sarcoma type/cell line | Vorinostat and etoposide | Sorafenib and topotecan | Dasatinib and MK-2206 | Dasatinib and triciribine | CI75 | CI95 | CI | SEM | | EOHSA | neg log Val | CI75 | CI95 | CI | SEM | | EOHSA | neg log Val | CI75 | CI95 | CI | SEM | | EOHSA | neg log Val | CI75 | CI95 | CI | SEM | | EOHSA | neg log Val |
| Ewing | | | | | | | | | | | | | | | | | | | | | | | | | | | | | A-673 | | | | | | | | | | | | | | | | | | | | | | 0.34 | 0.34 | 0.34 | 0.07 | 2 | 0.23 | 4.70 | RD-ES | | | | | | | | 1.00 | 1.19 | 1.10 | 0.07 | 2 | 0.046 | 1.12 | 0.18 | 0.18 | 0.18 | 0.03 | 2 | 0.23 | 4.40 | 0.19 | 0.17 | 0.18 | 0.08 | 3 | 0.28 | 4.71 | SK-ES-1 | 1.10 | 0.93 | 1.01 | 0.10 | 3 | 0.10 | 1.67 | 1.58 | 1.75 | 1.66 | 0.35 | 3 | 0.076 | 2.24 | 0.17 | 0.17 | 0.17 | 0.07 | 3 | 0.21 | 4.34 | 0.39 | 0.38 | 0.39 | 0.01 | 2 | 0.18 | 8.85 | Osteosarcoma | | | | | | | | | | | | | | | | | | | | | | | | | | | | | MNNG HOS | 0.78 | 0.95 | 0.86 | 0.27 | 3 | 0.08 | 1.62 | | | | | | | | 0.022 | 0.003 | 0.011 | | 1 | 0.17 | 4.10 | | | | | | | | U2-OS | 0.58 | 0.53 | 0.55 | 0.02 | 5 | 0.12 | 3.98 | 0.58 | 0.49 | 0.53 | 0.28 | 2 | 0.060 | 1.04 | 0.38 | 0.54 | 0.46 | 0.05 | 3 | 0.18 | 3.72 | 0.10 | 0.03 | 0.06 | | 1 | 0.36 | 7.94 | Rhabdoid | | | | | | | | | | | | | | | | | | | | | | | | | | | | | A-204 | 0.85 | 1.20 | 0.99 | 0.20 | 5 | 0.09 | 2.58 | 0.61 | 1.29 | 0.91 | 0.32 | 3 | 0.088 | 2.41 | 0.15 | 0.14 | 0.14 | | 1 | 0.38 | 4.49 | | | | | | | | Leiomyosarcoma | | | | | | | | | | | | | | | | | | | | | | | | | | | | | SK-LMS-1 | 0.69 | 0.68 | 0.67 | 0.10 | 3 | 0.09 | 2.23 | | | | | | | | 0.31 | 0.34 | 0.32 | 0.03 | 3 | 0.21 | 3.69 | 0.24 | 0.23 | 0.24 | 0.05 | 3 | 0.27 | 4.61 | SK-UT-1 | 0.73 | 0.68 | 0.70 | 0.17 | 3 | 0.11 | 5.39 | | | | | | | | 0.12 | 0.12 | 0.12 | 0.10 | 2 | 0.27 | 7.09 | 0.28 | 0.25 | 0.27 | | 1 | 0.18 | 3.82 | Liposarcoma | | | | | | | | | | | | | | | | | | | | | | | | | | | | | SW-872 | 0.53 | 0.38 | 0.45 | 0.15 | 3 | 0.19 | 3.00 | | | | | | | | 0.20 | 1.14 | 0.54 | 0.24 | 4 | 0.15 | 3.96 | | | | | | | | Fibrosarcoma | | | | | | | | | | | | | | | | | | | | | | | | | | | | | HT-1080 | 0.23 | 0.16 | 0.19 | 0.04 | 5 | 0.24 | 2.79 | | | | | | | | 0.39 | 0.76 | 0.57 | 0.17 | 3 | 0.18 | 2.87 | | | | | | | |
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