Fig. 4.

In-vitro growth inhibitory effect of multi-erbB inhibitors canertinib is enhanced in BRAF V600E cells in the presence of BRAF inhibitor vemurafenib. (a) BRAF mutant and WT cells were treated with 1 μmol/l vemurafenib for 3 days and cell proliferation was monitored using the MTT assay. Effective growth inhibitory effect of vemurafenib could only be seen in BRAF mutant cells A375 and M14, but not in BRAF WT SK-MEL147 and IgR3. (b) The in-vitro antitumor effect of canertinib was greatly increased by vemurafenib (1 μmo/l) only in BRAF mutant cells. Cells were treated with increasing concentrations of canertinib in the presence or absence of 1 μmol/l vemurafenib for 3 days followed by MTT assay. (c) The dose-dependent responses of BRAF mutant cells A375 and M14 towards vemurafenib was enhanced by increasing concentrations of canertinib. A375 and M14 cells were treated with increasing concentrations of vemurafenib in the presence or absence of canertinib (5 or 10 μmol/l) for 3 days followed by MTT assay. WT, wildtype.