Validation of the prediction result on ER positive breast cancer cell line MCF7.

(a) Seventeen agent pairs tested by experiment on MCF7 cell line. CI for each drug pair was summarized in a heat map. Green indicates synergy (CI<0.9); dark green indicates strong synergy (CI<0.3); yellow indicates additive (0.9<CI<1.1); and red indicates antagonism (CI>1.1). ‘4+1’, ‘3+2’, ‘2+3’, and ‘1+4’ indicate combinations of same drug pairs at four different concentration ratios: 4:1, 3:2, 2:3, and 1:4. The results summary table was rearranged according to the CI values in the order of ‘Strong synergy → synergy → Additive effect → Antagonism’. ^aThere involves single agent without MCF7 expression profile. (b) Five agent pairs reported in literatures. (c) Co-administrations of Erlotinib and Sorafenib inhibited tumour growth and dissemination in a zebrafish-based human cancer cell xenograft model. (I-VII) MCF-7 cells were labelled with red fluorescence for easy observation in the zebrafish tumour xenograft model. Compared with vehicle control treated embryos, Erlotinib combined with Sorafenib significantly inhibited tumour growth and dissemination in 4-dpi zebrafish embryos. White arrowheads indicate disseminated tumour foci. H, heart; L, liver. (VIII,IX) Quantification of tumour growth and numbers of disseminated tumour foci. Columns, mean; bars, s.e.m. (n=9; ANOVA). RFI, relative fluorescence intensity; dpi, days post injection. ns: not significant, *P value<0.05, **P value<0.01, ***P value<0.0001.