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+. Sn, nM for 96 hours Apoptosis was determined by 7-AAD and Annexin V- FLUOS staining with a FACScan. F: HCT116 cell cycle distribution after sorafenib 0.5 µM +, nM was measured by propidium iodide staining with a FACScan flow cytometer

H. Intracellular-accumulation-in-hct116-s, H. , H. , and H. Cells, D: Flow cytometric analysis of SN-38 intracellular accumulation in HCT116, SW48, SW620 and HT29 cells E: Flow cytometry analysis of SN-38 intracellular accumulation in HCT116-s, HCT116-SN6, HCT116-A2, HCT116-SN50 and HCT116-G7 cells after exposure to SN-38 alone or in combination with sorafenib. The SN-38+sorafenib values are relative to the SN-38 alone values (set to 1) in order to compare the fold change between conditions. F: Flow cytometry analysis of SN-38 intracellular accumulation in HCT116, SW48, SW620 and HT29 cells following exposure to SN-38 alone or in combination with sorafenib. The SN-38+sorafenib values are relative to the SN-38 alone values (set to 1) to compare the fold change between conditions. G: Western blot analysis of ABCG2 expression, HCT116-A2 and HCT116 SN50 treated with Sorafenib 0

S. Shluc, Protein loading is shown by GAPDH. B: Flow cytometric analysis of

I. Sorafenib, . Alone, and . Sorafenib-alone, Quantitative data were obtained using the G- Box from Syngene and the GenTools software B: The phosphorylation of p38 and ERK was verified by Western Blotting on protein extract from xenografts from 5 different mice. Equal loading is shown by Tubulin. Quantification of phospho-p38 (pp38) and phospho-ERK (pERK) relative to Tubulin. Histograms represent the mean of the 5 different mice for each treatment