Summary of the effect of tyrosine kinase inhibitor (TKI) and combinations on proliferation, cleaved caspase 3/7, cell cycle profile and phosphorylated status of receptor tyrosine kinase (RTK) and downstream targets in a panel of oesophago-gastric cell lines
| Cell line | Active RTK(s) | Drug target(s) | IC50 (95% CI) (nM) | Loss of phosphorylation status (for 1 μM drug concentration) |
|---|---|---|---|---|
| OE19 | EGFR, ErbB2, ErbB3 | Mek | 95 (34 to 263) | Erk |
| ErbB2/EGFR | 100 (39 to 120) | EGFR, ErbB2, Erk, Akt | ||
| EGFR | 6.6×103 (2.3×103 to 19.1×103) | No loss | ||
| MKN45 | EGFR, ErbB3, Met, Ret | Met | 5.58 (4.05 to 7.68) | EGFR, Met, ErbB2, Ret, Erk, Akt |
| Mek | 14 (0.4 to 46) | Erk | ||
| ErbB2/EGFR | 2.95×103 (1.74 to 4.99×103) | No loss | ||
| ErbB2/EGFR-Met | 9.7×103 (too wide) | EGFR, ErbB2, FGFR2, Met, Erk, Akt | ||
| Ret | Insensitive | EGFR, ErbB2, Met, Ret, Erk, Akt | ||
| ErbB2/EGFR-Met-Ret | Unclear | EGFR, ErbB2, Met, Ret, Erk, Akt | ||
| KATOIII | EGFR, ErbB3, FGFR2 | FGFR | 4.8 (3.4 to 6.7) | FGFR2, ErbB2, EGFR, Erk, Akt |
| ErbB2/EGFR-FGFR | 5.8 (3.9 to 8.4) | FGFR2, ErbB2, EGFR, Erk, Akt | ||
| Mek | 175 (89 to 342) | Erk | ||
| ErbB2/EGFR | 4.5×103 (2.2×103 to 9.4×103) | No loss | ||
| HSC39 | EGFR, ErbB3, Met, FGFR2 | ErbB2/EGFR -Met-FGFR | 2.4 (1.1 to 4.1) | FGFR2, Met, ErbB2, Erk, Akt |
| ErbB2/EGFR -FGFR | 2.9 (1.4 to 5.9) | FGFR2, Met, ErbB2, Erk, Akt | ||
| FGFR-Met | 3.2 (2.8 to 3.7) | FGFR2, Met, ErbB3, Erk, Akt | ||
| FGFR | 5.9 (4.8 to 7.3) | FGFR2, Met, ErbB2, Erk, Akt | ||
| Mek | 7.9 (2.1 to 2.9) | Erk | ||
| Met | 1.1×103 (0.1×103 to 10×103) | Met | ||
| ErbB2/EGFR-Met | 1.6×103 (1.2×103 to 2.0×103) | EGFR, Met, ErbB2 | ||
| ErbB2/EGFR | 2.1×103(1.7×103 to 2.7×103) | No loss | ||
| OE33 | EGFR, ErbB2, ErbB3, Ret, Met | Mek | 9.1 (3.7 to 22) | Erk |
| ErbB2/EGFR -Met-FGFR-Ret | 93 (70 to 124) | Akt, Erk, EGFR, Met, ErbB2/3, ret | ||
| ErbB2/EGFR-Met | 124 (80 to 193) | Akt, EGFR, P-Met, ErbB3, ret | ||
| ErbB2/EGFR-FGFR | 2.4×103(1.6×103 to 7.1×103) | None lost | ||
| Met | 3.0×103(1.9×103 to 4.8×103) | Akt, EGFR, Met, ErbB2, ret | ||
| ErbB2/EGFR-FGFR-Met | 10.1×103(7.4×103 to 13.8×106) | Akt, EGFR, Met, ErbB2, ret | ||
| EGFR | 89.8×103(1.4×103 to 5.6×106) | EGFR | ||
| Ret | 117×103(10.0×103 to 137×103) | No loss | ||
| ErbB2/EGFR | 126×103(2.5×103 to 6.3×103) | No loss | ||
| FGFR | 280×103(very wide) | No loss |
Western blots were probed for total EGFR, ErbB2, ErbB3, Ret, Met, FGFR, Erk and Akt as well for their phosphorylated species. Only species where loss of phosphorylation was noted are indicated in the loss of phosphorylation status column. The most efficacious combination of TKIs is indicated in bold. Proliferation assays were run for all single drug targets or combinations. Cleaved caspase 3/7 assay and flow cytometry were run for all single drug targets with IC50 in the nm range and on drug combinations if they improved significantly on single drug targets. For assays on combinations we selected the minimum number of drugs that were effective.