JZL184 reduces skeletal tumour growth, metastasis and cachexia and improves survival in mice. (a) Effects of JZL184 (16 mg/kg, thrice weekly) on in vivo tumour area (% tissue area) in the tibial metaphysis of mice after intra-cardiac injection of osteotropic human prostate PC3-BT cells (n = 16, 32 days) and MDA-231-BT (n = 16, 55 days) into BALB/c -nu/nu athymic mice (8 weeks old), or intra-tibial injection of the human KHOS and mouse MOS-J osteosarcoma into NMRI athymic nude and C57BL/6j mice, respectively (5 weeks old, n = 7, 33 days). (b-c) Representative photomicrographs of microCT scan of the trabecular compartment and long bone of the tibial metaphysis of mice after the injection of human osteotropic prostate PC3-BT cells (b, scale bar = 1 mm) and KHOS osteosarcoma (c, scale bar = 5 mm), respectively. Arrowheads denote tumour body. (d) Development of bone metastasis in mice after the injection of human osteotropic prostate PC3-BT cells as assessed by changes in photon intensity (photo/s) between day 17 and 24 post cell inoculation. (e) Development of lung metastasis in mice after the injection of human KHOS osteosarcoma as assessed by the number of macroscopic metastases. (f) Survival of mice treated with JZL184 (16 mg/kg, thrice weekly) for 33 days after para-tibial injections of the human KHOS cells (n = 7–8) from the experiment described in panels F–H. Values are mean ± SD; * p < .05.