Fig. 6.

Endothelial Dll4 over expression improves tumor drug delivery and reduces metastasis formation. a, b doxorubicin administration (Dx-D4BE) and Dll4 over-expression in endothelial cells (D4OE) retarded xenograft volume increase after subcutaneous LLC implantation in D4BE and D4OE littermates. Doxorubicin administration to Dll4 endothelial overexpressing mice (Dx-D4OE) resulted in the highest tumor growth regression. Upon endpoint lungs were dissected and metastatic foci were counted under a dissection microscope. Both D4OE and Dx-D4BE mice displayed reduced numbers of lung metastasis but Dx-D4OE mice had no detectable lung metastatic foci (c). d Primary tumor samples were also recovered at endpoint to evaluate doxorubicin concentration. Doxorubicin accumulation in the primary tumor was increased by 60% in D4OE mice when compared to D4BE. Error bars represent SEM. *, P < 0.05was considered significant. Results are representative of n = 10 per mice group