Figure 1.

Small-molecule inhibition of the FGFRs inhibits cell growth and induces apoptosis. (a) MTT cell viability assays of HCT116, HKH2, RKO and LS174T cells treated for 48 h with increasing concentrations of BGJ398. Absorbance was measured at 570 nM. (b) Annexin V/PI flow cytometric analysis was used to measure the levels of apoptosis in the HCT116 cell line following treatment with IC_{30 (48 h)} doses of 5-FU or oxaliplatin for 48 h and co-treatment with IC_{30 (48 h)} doses of BGJ398 for a further 24 h. Significance was determined by two-way analysis of variance. Results are presented as mean values±S.E.M. for three replicate experiments (**P<0.01, ***P<0.001). (c) MTT cell viability assay results showing percentage of surviving HCT116 cells transfected for 24 h with siFGFR1, siFGFR2, siFGFR3 or siFGFR4 before treatment with solvent control or IC_{30 (48 h)} doses of 5-FU or oxaliplatin. (d) Immunoprecipitation using a phospho-tyrosine antibody was performed on HCT116 cells pre-treated with an IC_{50 (48 h)} dose of BGJ398 for 24 h followed by a further IC_{50 (48 h)} dose of BGJ398±100 ng/ml of FGF19 before immunoblotting for FGFR4