<i>In vivo</i> effects of tivantinib and ZA alone and in combination in a therapeutic schedule of bone metastases.

<p>The bone metastatic 1833/TGL cells were injected into the left cardiac ventricle of 4-week old athymic nude mice (5×10⁵ cells/mouse). When bone metastases were detectable (11 days after cell implant), implanted animals were randomized into 4 groups of 10 mice each: controls treated with vehicle PEG 400∶20% vitamin E TPGS solution (60∶40) or treated groups administered with tivantinib alone (300 mg/Kg), ZA (100 mg/Kg) alone and combination of tivantinib plus ZA. Both vehicle and tivantinib were administered daily <i>per os</i> starting 13 days after implant until the end of the experiment. ZA was administered i.p. every 2 days starting 13 days after implant till the end of the experiment. (<b>A</b>) Representative optical scanning in the supine position for each group 27 days after tumor implant. The intensity of the BLI signal, measured as total photon flux, is shown as a pseudo-color scale bar. Numbers at the left bottom of the images represent the number of mice. (<b>B</b>) At the indicated times after xenografting, the BLI signal was captured and the growth kinetics of right and left hindlimb metastasis for each group were expressed in the graph as mean value of total photon counts from the hindlimbs of animals. Data are presented as mean value ± SE; <b>*</b>, p<0.05 tivantinib+ZA vs tivantinib. (<b>C</b>) Representative volume-rendered micro-CT images of osteolytic bone metastases obtained 27 days after xenografting are shown. Red circles indicate osteolysis and the numbers at the bottom of the images represent the number of mice. (D) Kaplan–Meyer curves of vehicle and treated groups.