Research Paper Volume 8, Issue 5 pp 958—973

Preclinical validation of a novel compound targeting p70S6 kinase in breast cancer

class="figure-viewer-img"

Figure 6. FS-115 is well tolerated and efficiently counteracts metastatic spread to distant organs. (A) Schematic representation of the experimental workflow used for the metastasis formation experiment. Mice were intracardiacally injected with MDA-MB-231-luc cells (1×105) and imaged at the end-point of study (70 days after inoculation). (B) Table describes the different experimental groups in which mice were subdivided to test different FS-115 concentrations and different treatment schedules. Number of death, percentages of lung, liver and brain metastasis incidence, calculated at day 70 in each group, are also indicated. (C) Graph reports the total flux (photons/sec) in the lungs extracted from mice of the different experimental groups. Mice were injected with D-luciferin before being culled, and then lungs imaged using a Xenogen IVIS machine. (D) Pictures show the lungs from two representative experimental groups (Group 2, Vehicle QD, 70 days and Group 6, FS-115 125mg/kg, BID, 70 days). (E) Same as in (C), except that livers were measured. (F) Same as in (C), except that brains were measured. (G) Graph reports the animal weight, expressed as percentage of initial bodyweight, in three representative experimental groups (Group 2, Vehicle QD, 70 days; Group 4 FS-115 250mg/kg, QD, 70 days; and Group 6, FS-115 125mg/kg, BID, 70 days). Bodyweight was annotated daily and used as a measure of drug tolerance. Group 4 is significantly different from Group 2 from 12 days of treatment. Group 6 is significantly different from Group 2 from 14 days of treatment. Group 4 is significantly different from Group 6 from 21 days of treatment. In all cases, differences were considered significant when p<0.05 (*) and calculated by two tailed t-test.